Otto Paulsen - Academia.edu (original) (raw)

Papers by Otto Paulsen

Scandinavian Journal of Infectious Diseases, 1981

Journal of chromatography, Jan 25, 1987

A method based on column liquid chromatography was developed for determination of plasma concentr... more A method based on column liquid chromatography was developed for determination of plasma concentrations of erythromycin. PRP-1, a polymeric type of packing material suitable for chromatography and amperometric detection at high pH, was used. The effect of pH on the column performance and on the electrochemical response was studied. A pH of ca. 10 was found to be optimal. After extraction with tert.-butyl methyl ether, plasma concentrations down to 0.2 mumol/l could be measured, using automated sample injection. Oleandomycin was used as internal standard. The method was used for determination of plasma concentrations in a pharmacokinetic study under steady-state conditions.

A number of new antibiotics have lately become available for treatment of lower respiratory tract... more A number of new antibiotics have lately become available for treatment of lower respiratory tract infections in out-patients. The new drugs are generally more expensive than the older ones, which might be justified by better effects, improved safety, or by other advantages. In this study, a retrospective economic analysis has been made using data from a previous trial comparing a new macrolide, roxithromycin, with an older 1, erythromycin stearate in the treatment of lower respiratory tract infections. The trial was multicentre, double blind, randomized and comparative. There were no significant differences in efficacy between treatments, although the cure rate was higher for roxithromycin, 85% vs 79% for erythromycin. 20/39 of the erythromycin-treated patients reported adverse events, vs 7/40 roxithromycin-treated subjects, a highly significant difference. More detailed information was obtained by reviewing the medical records of the participants, and from questionnaires distributed to the 3 centres that had included patients in the trial. Additional visits were found necessary for 4 patients treated with erythromycin and for 1 using roxithromycin. Using the healing rates in the present investigation, and including costs for initial drug treatments, second consultations, and failed therapy, average cost-effectiveness (SEK/patient cured) was 409 for roxithromycin-treated patients, and 488 for erythromycin-treated. Roxithromycin should then be cheaper than erythromycin stearate. With the same healing rate, roxithromycin would be less cost-effective, but indirect costs and effects on quality of life are not then taken into account.

European Journal of Respiratory Diseases, Mar 1, 1987

Metabolic interactions between theophylline and several other drugs have been described in a numb... more Metabolic interactions between theophylline and several other drugs have been described in a number of studies. They may be of importance because of the narrow therapeutic range of theophylline. A significant risk for interactions has been considered to exist only with drugs metabolized by oxidative enzyme systems, and thus is not expected to occur with isoniazid. However, an increased clearance of theophylline with oral isoniazid medication has been reported. On the other hand, we found a significant increase in plasma levels of intravenously infused theophylline, and a corresponding decrease in plasma clearance of theophylline, when isoniazid was administered orally, compared to similar infusions in these individuals without concomitant isoniazid medication. The effect was seen irrespective of acetylator status. In five of the seven subjects an increase of isoniazid half-life and AUC was seen with theophylline, but this increase was not statistically significant.

The cure rate of acute uncomplicated urinary tract infection in general practice using 3 differen... more The cure rate of acute uncomplicated urinary tract infection in general practice using 3 different treatment regimens, was studied in a randomized, multicenter trial. Patients were assigned to receive either cefadroxil 1 g once daily for 3 or 7 days or amoxycillin 375 mg t.i.d. for 7 days. 310 patients entered the study, of whom 230 could be evaluated according to the protocol. Two thirds of the cases were due to infections with Escherichia coli and about one fourth to Staphylococcus saprophyticus. No statistically significant differences in cure rates between the 3 regimens could be demonstrated neither at 1 week nor at 5 weeks of follow-up. The frequency of adverse reactions was low and similar in each treatment group.

Scandinavian journal of infectious diseases, 1977

A case of herpes encephalitis diagnosed by brain biopsy and treated with 5-iodo-2-deoxyuridine (I... more A case of herpes encephalitis diagnosed by brain biopsy and treated with 5-iodo-2-deoxyuridine (IDU) is presented. The infection occurred in a previously well 19-year-old female patient. Plasma and cerebrospinal fluid (CSF) uptake of the substance was determined using 125I labelled IDU. Top CSF levels of IUD and metabolites of less than 4 microgram/ml, about 1/10 of the corresponding plasma level, were obtained after 6 hours of continuous infusion. The result is discussed and compared with a similar study made on 5 healthy beagle dogs where in addition the levels obtained in various parts of the brain were determined. In the animal experiment a mean value of 2.5 microgram/ml of IDU and metabolites was obtained in the CSF after 8 hours, less than 1/20 of the plasma level. The levels in brain tissue were only slightly higher than in the CSF. The causes of therapeutic failures with IDU treatment are discussed.

Therapeutic Drug Monitoring, 1989

The effect of concomitant treatment with omeprazole (20 mg/day) on the plasma concentration and a... more The effect of concomitant treatment with omeprazole (20 mg/day) on the plasma concentration and anticoagulation effect of warfarin was studied in 21 young healthy men. An initial three weeks' treatment with warfarin alone was administered to determine the doses required for the subjects' vitamin K-dependent coagulation factors to fall within 10-20% of the normal range, as determined by the Trombotest. Omeprazole and placebo were then administered concomitantly with warfarin for 2 weeks each in a double-blind, randomized, crossover fashion. Plasma concentrations of (R)- and (S)-warfarin, and Trombotest values were measured daily on weekdays throughout the crossover period. Omeprazole had no apparent effect on the mean (S)-warfarin plasma concentration (379 ng/ml with, versus 387 ng/ml without, omeprazole), but caused a slight (12%) although statistically significant increase in the mean (R)-warfarin concentration from 490 to 548 ng/ml (95% confidence interval for difference of means: 28-88). The Trombotest values exhibited large inter- and intrasubject variability during both omeprazole and placebo treatment; however, there was a small, although statistically significant decrease in the mean value from 21.1% without to 18.7% with omeprazole treatment (95% CI for difference of means: -4.6- -0.1). Those subjects with Trombotest values nearest the therapeutic range (5-15%) exhibited less change during omeprazole treatment, and no changes occurred that required a change in warfarin dosing. The interaction of omeprazole with warfarin was attributed to a stereoselective inhibition of the hepatic metabolism of the less potent (R)-warfarin enantiomer. The small effect of omeprazole on the anticoagulation activity of warfarin is not likely to be of clinical importance.

Therapeutic Drug Monitoring, 1989

The influence of terodiline (25 mg b.i.d.) on the anticoagulant effect and plasma levels of warfa... more The influence of terodiline (25 mg b.i.d.) on the anticoagulant effect and plasma levels of warfarin enantiomers was studied in 23 young healthy male volunteers. Racemic warfarin was first given for 24 days to determine the doses required for the subject's vitamin K-dependent coagulation factors to fall within 10-20% of the normal range, as determined by the Thrombotest. During continuous warfarin treatment (mean daily dose 5.3 mg, range 2.5-9.4 mg), terodiline or placebo was given for two weeks in a randomized and double-blind fashion, and then the drugs were crossed over and given for another two weeks. Terodiline did not influence the anticoagulant effect of warfarin or the plasma levels of the warfarin enantiomers. The results indicate that it should not be necessary to monitor patients on combined therapy with terodiline and warfarin more frequently than patients on warfarin monotherapy.

Scandinavian Journal of Infectious Diseases, 2002

Intravenous administration of antibiotics is a known risk factor for infusion phlebitis. We have ... more Intravenous administration of antibiotics is a known risk factor for infusion phlebitis. We have previously demonstrated differences in cell toxicity for 4 antibiotics. Clinical experience indicates that antibiotics differ in their tendency to cause phlebitis. The present study was done prospectively on 550 patients with 1386 peripheral venous catheters. The incidence of phlebitis was 18.5% with antibiotics and 8.8% without (odds ratio 2.34). Dicloxacillin (odds ratio 5.74) and erythromycin (odds ratio 5.33) had the greatest tendency to cause phlebitis in univariate, multivariate and Cox regression analyses. Benzylpenicillin, cefuroxime and cloxacillin were also associated with a greater risk of phlebitis, whereas ampicillin, imipenem/cilastatin, clindamycin, netilmicin and vancomycin were not. Other risk factors were the site of insertion and age 51-60 y. Medication with warfarin was found to be protective, but not with aspirin. Treatment with low molecular weight heparin reduced the risk of phlebitis, but the difference was not significant. With regard to when antibiotics were given, the day-specific risk increased between Days 1 and 2, but no further on subsequent days. The hypothesis that antibiotics differ in their tendency to cause phlebitis was confirmed.

Scandinavian Journal of Infectious Diseases, 1995

16 patients with chronic hepatitis C virus (HCV) infection were treated with a combination of int... more 16 patients with chronic hepatitis C virus (HCV) infection were treated with a combination of interferon-alpha and ribavirin for 24 weeks in an open study. One patient declined further treatment due to depression after week 16 and did not complete further follow-up. A moderate decline was observed in hemoglobin and an increase in bilirubin level both reversible after discontinuing the treatment. 24 weeks after treatment cessation 9/15 (60%) evaluable patients had complete clearance of HCV-RNA as measured with PCR. HCV genotype did not seem to be correlated with response, but patients with sustained response to treatment had a significantly reduced number of HCV RNA copies/ml serum at treatment start compared with the other patients. These findings support the promising results of this combination therapy noted in other pilot studies.

Scandinavian Journal of Infectious Diseases, 1989

From studies on prophylaxis against experimental streptococcal endocarditis using amoxycillin in ... more From studies on prophylaxis against experimental streptococcal endocarditis using amoxycillin in a single dose, it has been deduced that serum concentrations above 0.12 mg/l should be maintained for at least 10 h after antibiotic administration. Since concentrations above this level are reported to occur following an oral dose of 3 g of amoxycillin, this doses for prophylaxis has become widely accepted in USA and the UK, and presently also in Sweden. Nevertheless, in individuals who cannot tolerate a high single dose of amoxycillin, there is need for an alternative dosage regimen. In the present study, we have compared the pharmacokinetics in 12 healthy volunteers, of a single dose of 3 g of amoxycillin with those of 1 g as single dose or combined with 1 g of probenecid. The combination resulted in an AUC twice as large as that achieved after 1 g of amoxycillin, and was slightly, but not significantly, larger than that after 3 g. However, amoxycillin concentrations above 0.12 mg/l were sustained for almost 14 h with the combination as compared to 10.4 hours following 3 g of amoxycillin only (p less than 0.001). Thus, the combination should be a convenient alternative in patients unable to tolerate a higher oral dose of amoxycillin, and in situations when an antibacterial effect of longer duration is desired.

Scandinavian Journal of Infectious Diseases, 1989

The absorption of ampicillin esters is reported to decrease when gastric acidity is inhibited bec... more The absorption of ampicillin esters is reported to decrease when gastric acidity is inhibited because of hydrolysis of the esters, or by lowered solubility at a higher pH. No such information on the hydroxylated derivative amoxycillin is available. This was investigated in 8 fasting volunteers, who received 800 mg bacampicillin or 1000 mg amoxycillin on 4 study days, separated by at least 1 week. Each ampicillin derivative was administered on 1 occasion as a single drug, and on another after 1 week's pretreatment with the potent acid inhibitor omeprazole. Bacampicillin was absorbed more rapidly than amoxycillin, and serum peak concentrations were higher. After induced hypoacidity, peak concentrations of both antibiotics appeared to be slightly delayed, and those of bacampicillin significantly reduced. Nevertheless, both the areas under the plasma concentration curves, and the half lives of elimination of the antibiotics were unaffected. Hypoacidity as such does not reduce the bioavailability of amoxycillin or bacampicillin.

Scandinavian Journal of Infectious Diseases, 1997

A number of new antibiotics have lately become available for treatment of lower respiratory tract... more A number of new antibiotics have lately become available for treatment of lower respiratory tract infections in out-patients. The new drugs are generally more expensive than the older ones, which might be justified by better effects, improved safety, or by other advantages. In this study, a retrospective economic analysis has been made using data from a previous trial comparing a new macrolide, roxithromycin, with an older 1, erythromycin stearate in the treatment of lower respiratory tract infections. The trial was multicentre, double blind, randomized and comparative. There were no significant differences in efficacy between treatments, although the cure rate was higher for roxithromycin, 85% vs 79% for erythromycin. 20/39 of the erythromycin-treated patients reported adverse events, vs 7/40 roxithromycin-treated subjects, a highly significant difference. More detailed information was obtained by reviewing the medical records of the participants, and from questionnaires distributed to the 3 centres that had included patients in the trial. Additional visits were found necessary for 4 patients treated with erythromycin and for 1 using roxithromycin. Using the healing rates in the present investigation, and including costs for initial drug treatments, second consultations, and failed therapy, average cost-effectiveness (SEK/patient cured) was 409 for roxithromycin-treated patients, and 488 for erythromycin-treated. Roxithromycin should then be cheaper than erythromycin stearate. With the same healing rate, roxithromycin would be less cost-effective, but indirect costs and effects on quality of life are not then taken into account.

Scandinavian Journal of Infectious Diseases, 2003

Ever since dicloxacillin and cloxacillin were introduced in the 1960s, it has been known that the... more Ever since dicloxacillin and cloxacillin were introduced in the 1960s, it has been known that they are associated with a high incidence of infusion phlebitis. Some in vitro studies and clinical experience have indicated that dicloxacillin is the more vessel-irritating of the 2 drugs. In this prospective observational study on 39 patients with 111 peripheral venous catheters (PVCs), the incidence of infusion phlebitis was compared between these 2 drugs. The incidence of phlebitis was 38% with dicloxacillin and 21% with cloxacillin; which, compared by logistic regression with other risk factors as covariates, was significant [odds ratio 5.06, 95% confidence interval (95% CI) 1.45-17.60]. Since the duration of catheterization is also an important risk factor, Cox regression was performed, and the difference between the 2 drugs was still significant (proportional hazard rate 3.48, 95%, CI 1.64-7.38). The only other significant risk factor found in the study was the insertion site; the risk was higher in PVCs inserted in the forearm/antecubital fossa than in the hand/wrist. The infusion time and dilution of the infusate were not significant risk factors.

Journal of Infusion Nursing, 2004

This questionnaire study was set up to assess the perceptions of risk factors for infusion phlebi... more This questionnaire study was set up to assess the perceptions of risk factors for infusion phlebitis among Swedish nurses, as their concepts of these factors may influence the incidence. A majority of the nurses believed that insertion of a peripheral venous catheter in the forearm and catheter rotation within 48 hours was protective. These measures are not supported in recent studies and guidelines. Surveillance of the educational level of staff, who insert peripheral venous catheters, is an important tool for reducing the incidence of infusion phlebitis.

Pharmacology & Toxicology, 1987

The effect of intravenously administered ampicillin on plasma levels and renal clearance of enpro... more The effect of intravenously administered ampicillin on plasma levels and renal clearance of enprofylline was investigated in seven young and six elderly volunteers. On one occasion, each subject received 2 g of ampicillin intravenously, and serum concentrations of ampicillin were followed for 4 hours. On a separate occasion, a loading infusion of enprofylline was administered over 60 min., aiming at a plasma level of 2 micrograms/ml, and followed by a maintenance infusion. During this an infusion of 2 g of ampicillin was given for 10 min., and subsequently, renal clearance and plasma levels of enprofylline were followed for 4 hours. Plasma enprofylline levels increased significantly in the subjects after ampicillin infusion, but the effects on renal clearance of enprofylline were not statistically significant. The magnitude of the effects on enprofylline plasma levels and renal clearance from high doses of ampicillin do not suggest that interaction with beta-lactam antibiotics will be a serious problem for patients on enprofylline treatment.

Pharmacology & Toxicology, 1995

Intravenous administration of antibiotics often causes local pain and thrombophlebitis at the sit... more Intravenous administration of antibiotics often causes local pain and thrombophlebitis at the site of injection. An in vitro model that could predict these effects would be of great value. In this study the effects of four antibiotics, benzylpenicillin, cefuroxime, dicloxacillin and erythromycin, have been evaluated on three types of endothelial cells in culture. The cell types employed were primary culture from human umbilical vein, primary culture from bovine aorta, and the cell line EA-hy 926, a hybride endothelial cell. These cells were exposed to antibiotics for 24 hr and subsequently toxic effects on cells were evaluated by three different assays. Benzylpenicillin was atoxic in all types of cells and in all assays, in contrast to the other antibiotics. The other three antibiotics exerted dose dependent toxic effects in all investigated cells when DNA-synthesis and total cell protein were used as toxicity assays but the results varied between the cell types. There were no significant differences between the effects of cefuroxime, dicloxacillin and erythromycin on bovine endothelial cells. In the other cell types, however, there were significant differences between some drugs but the outcome depended on the cell type. It is concluded that it is possible to show differences between the effect of antibiotics on endothelial cells, but the result depends on the cell type employed.

Pharmacology & Toxicology, 2008

The irritating effect of parenterally administered antibiotics on vessels is a common clinical pr... more The irritating effect of parenterally administered antibiotics on vessels is a common clinical problem. In a previous study we found that solutions of three commonly used antibiotics, cefuroxime, erythromycin and dicloxacillin, exerted cytotoxic effects on endothelial cells after 24 hr exposure. In contrast benzylpenicillin did not have such effects. In the present study, endothelial cells of different origin were exposed to these four antibiotics at higher concentrations than in the previous investigation but only for 5, 30 and 60 min. Incorporation of 3 H-thymidine in the cells as a measurement of DNA synthesis was used as cytotoxic assay. A concentration-dependent and time-related inhibition was found after exposure to erythromycin and dicloxacillin but not after exposure to cefuroxime and benzylpenicillin. The effects were similar on the three different cell types used in the experiments. This study demonstrates that the cytotoxic effects differ even after short-term exposure to the antibiotics. In contrast to the previous study, cefuroxime lacks cytotoxicity when endothelial cells are exposed for less than one hour. The short-term exposition model used in this study should be more predictive as it mimics in vivo conditions better.

Archives Of Physiology And Biochemistry, 1985

The cure rate of acute uncomplicated urinary tract infection in general practice using 3 differen... more The cure rate of acute uncomplicated urinary tract infection in general practice using 3 different treatment regimens, was studied in a randomized, multicenter trial. Patients were assigned to receive either cefadroxil 1 g once daily for 3 or 7 days or amoxycillin 375 mg t.i.d. for 7 days. 310 patients entered the study, of whom 230 could be evaluated according to the protocol. Two thirds of the cases were due to infections with Escherichia coli and about one fourth to Staphylococcus saprophyticus. No statistically significant differences in cure rates between the 3 regimens could be demonstrated neither at 1 week nor at 5 weeks of follow-up. The frequency of adverse reactions was low and similar in each treatment group.

Scandinavian Journal of Infectious Diseases, 1981

Journal of chromatography, Jan 25, 1987

A method based on column liquid chromatography was developed for determination of plasma concentr... more A method based on column liquid chromatography was developed for determination of plasma concentrations of erythromycin. PRP-1, a polymeric type of packing material suitable for chromatography and amperometric detection at high pH, was used. The effect of pH on the column performance and on the electrochemical response was studied. A pH of ca. 10 was found to be optimal. After extraction with tert.-butyl methyl ether, plasma concentrations down to 0.2 mumol/l could be measured, using automated sample injection. Oleandomycin was used as internal standard. The method was used for determination of plasma concentrations in a pharmacokinetic study under steady-state conditions.

A number of new antibiotics have lately become available for treatment of lower respiratory tract... more A number of new antibiotics have lately become available for treatment of lower respiratory tract infections in out-patients. The new drugs are generally more expensive than the older ones, which might be justified by better effects, improved safety, or by other advantages. In this study, a retrospective economic analysis has been made using data from a previous trial comparing a new macrolide, roxithromycin, with an older 1, erythromycin stearate in the treatment of lower respiratory tract infections. The trial was multicentre, double blind, randomized and comparative. There were no significant differences in efficacy between treatments, although the cure rate was higher for roxithromycin, 85% vs 79% for erythromycin. 20/39 of the erythromycin-treated patients reported adverse events, vs 7/40 roxithromycin-treated subjects, a highly significant difference. More detailed information was obtained by reviewing the medical records of the participants, and from questionnaires distributed to the 3 centres that had included patients in the trial. Additional visits were found necessary for 4 patients treated with erythromycin and for 1 using roxithromycin. Using the healing rates in the present investigation, and including costs for initial drug treatments, second consultations, and failed therapy, average cost-effectiveness (SEK/patient cured) was 409 for roxithromycin-treated patients, and 488 for erythromycin-treated. Roxithromycin should then be cheaper than erythromycin stearate. With the same healing rate, roxithromycin would be less cost-effective, but indirect costs and effects on quality of life are not then taken into account.

European Journal of Respiratory Diseases, Mar 1, 1987

Metabolic interactions between theophylline and several other drugs have been described in a numb... more Metabolic interactions between theophylline and several other drugs have been described in a number of studies. They may be of importance because of the narrow therapeutic range of theophylline. A significant risk for interactions has been considered to exist only with drugs metabolized by oxidative enzyme systems, and thus is not expected to occur with isoniazid. However, an increased clearance of theophylline with oral isoniazid medication has been reported. On the other hand, we found a significant increase in plasma levels of intravenously infused theophylline, and a corresponding decrease in plasma clearance of theophylline, when isoniazid was administered orally, compared to similar infusions in these individuals without concomitant isoniazid medication. The effect was seen irrespective of acetylator status. In five of the seven subjects an increase of isoniazid half-life and AUC was seen with theophylline, but this increase was not statistically significant.

The cure rate of acute uncomplicated urinary tract infection in general practice using 3 differen... more The cure rate of acute uncomplicated urinary tract infection in general practice using 3 different treatment regimens, was studied in a randomized, multicenter trial. Patients were assigned to receive either cefadroxil 1 g once daily for 3 or 7 days or amoxycillin 375 mg t.i.d. for 7 days. 310 patients entered the study, of whom 230 could be evaluated according to the protocol. Two thirds of the cases were due to infections with Escherichia coli and about one fourth to Staphylococcus saprophyticus. No statistically significant differences in cure rates between the 3 regimens could be demonstrated neither at 1 week nor at 5 weeks of follow-up. The frequency of adverse reactions was low and similar in each treatment group.

Scandinavian journal of infectious diseases, 1977

A case of herpes encephalitis diagnosed by brain biopsy and treated with 5-iodo-2-deoxyuridine (I... more A case of herpes encephalitis diagnosed by brain biopsy and treated with 5-iodo-2-deoxyuridine (IDU) is presented. The infection occurred in a previously well 19-year-old female patient. Plasma and cerebrospinal fluid (CSF) uptake of the substance was determined using 125I labelled IDU. Top CSF levels of IUD and metabolites of less than 4 microgram/ml, about 1/10 of the corresponding plasma level, were obtained after 6 hours of continuous infusion. The result is discussed and compared with a similar study made on 5 healthy beagle dogs where in addition the levels obtained in various parts of the brain were determined. In the animal experiment a mean value of 2.5 microgram/ml of IDU and metabolites was obtained in the CSF after 8 hours, less than 1/20 of the plasma level. The levels in brain tissue were only slightly higher than in the CSF. The causes of therapeutic failures with IDU treatment are discussed.

Therapeutic Drug Monitoring, 1989

The effect of concomitant treatment with omeprazole (20 mg/day) on the plasma concentration and a... more The effect of concomitant treatment with omeprazole (20 mg/day) on the plasma concentration and anticoagulation effect of warfarin was studied in 21 young healthy men. An initial three weeks' treatment with warfarin alone was administered to determine the doses required for the subjects' vitamin K-dependent coagulation factors to fall within 10-20% of the normal range, as determined by the Trombotest. Omeprazole and placebo were then administered concomitantly with warfarin for 2 weeks each in a double-blind, randomized, crossover fashion. Plasma concentrations of (R)- and (S)-warfarin, and Trombotest values were measured daily on weekdays throughout the crossover period. Omeprazole had no apparent effect on the mean (S)-warfarin plasma concentration (379 ng/ml with, versus 387 ng/ml without, omeprazole), but caused a slight (12%) although statistically significant increase in the mean (R)-warfarin concentration from 490 to 548 ng/ml (95% confidence interval for difference of means: 28-88). The Trombotest values exhibited large inter- and intrasubject variability during both omeprazole and placebo treatment; however, there was a small, although statistically significant decrease in the mean value from 21.1% without to 18.7% with omeprazole treatment (95% CI for difference of means: -4.6- -0.1). Those subjects with Trombotest values nearest the therapeutic range (5-15%) exhibited less change during omeprazole treatment, and no changes occurred that required a change in warfarin dosing. The interaction of omeprazole with warfarin was attributed to a stereoselective inhibition of the hepatic metabolism of the less potent (R)-warfarin enantiomer. The small effect of omeprazole on the anticoagulation activity of warfarin is not likely to be of clinical importance.

Therapeutic Drug Monitoring, 1989

The influence of terodiline (25 mg b.i.d.) on the anticoagulant effect and plasma levels of warfa... more The influence of terodiline (25 mg b.i.d.) on the anticoagulant effect and plasma levels of warfarin enantiomers was studied in 23 young healthy male volunteers. Racemic warfarin was first given for 24 days to determine the doses required for the subject's vitamin K-dependent coagulation factors to fall within 10-20% of the normal range, as determined by the Thrombotest. During continuous warfarin treatment (mean daily dose 5.3 mg, range 2.5-9.4 mg), terodiline or placebo was given for two weeks in a randomized and double-blind fashion, and then the drugs were crossed over and given for another two weeks. Terodiline did not influence the anticoagulant effect of warfarin or the plasma levels of the warfarin enantiomers. The results indicate that it should not be necessary to monitor patients on combined therapy with terodiline and warfarin more frequently than patients on warfarin monotherapy.

Scandinavian Journal of Infectious Diseases, 2002

Intravenous administration of antibiotics is a known risk factor for infusion phlebitis. We have ... more Intravenous administration of antibiotics is a known risk factor for infusion phlebitis. We have previously demonstrated differences in cell toxicity for 4 antibiotics. Clinical experience indicates that antibiotics differ in their tendency to cause phlebitis. The present study was done prospectively on 550 patients with 1386 peripheral venous catheters. The incidence of phlebitis was 18.5% with antibiotics and 8.8% without (odds ratio 2.34). Dicloxacillin (odds ratio 5.74) and erythromycin (odds ratio 5.33) had the greatest tendency to cause phlebitis in univariate, multivariate and Cox regression analyses. Benzylpenicillin, cefuroxime and cloxacillin were also associated with a greater risk of phlebitis, whereas ampicillin, imipenem/cilastatin, clindamycin, netilmicin and vancomycin were not. Other risk factors were the site of insertion and age 51-60 y. Medication with warfarin was found to be protective, but not with aspirin. Treatment with low molecular weight heparin reduced the risk of phlebitis, but the difference was not significant. With regard to when antibiotics were given, the day-specific risk increased between Days 1 and 2, but no further on subsequent days. The hypothesis that antibiotics differ in their tendency to cause phlebitis was confirmed.

Scandinavian Journal of Infectious Diseases, 1995

16 patients with chronic hepatitis C virus (HCV) infection were treated with a combination of int... more 16 patients with chronic hepatitis C virus (HCV) infection were treated with a combination of interferon-alpha and ribavirin for 24 weeks in an open study. One patient declined further treatment due to depression after week 16 and did not complete further follow-up. A moderate decline was observed in hemoglobin and an increase in bilirubin level both reversible after discontinuing the treatment. 24 weeks after treatment cessation 9/15 (60%) evaluable patients had complete clearance of HCV-RNA as measured with PCR. HCV genotype did not seem to be correlated with response, but patients with sustained response to treatment had a significantly reduced number of HCV RNA copies/ml serum at treatment start compared with the other patients. These findings support the promising results of this combination therapy noted in other pilot studies.

Scandinavian Journal of Infectious Diseases, 1989

From studies on prophylaxis against experimental streptococcal endocarditis using amoxycillin in ... more From studies on prophylaxis against experimental streptococcal endocarditis using amoxycillin in a single dose, it has been deduced that serum concentrations above 0.12 mg/l should be maintained for at least 10 h after antibiotic administration. Since concentrations above this level are reported to occur following an oral dose of 3 g of amoxycillin, this doses for prophylaxis has become widely accepted in USA and the UK, and presently also in Sweden. Nevertheless, in individuals who cannot tolerate a high single dose of amoxycillin, there is need for an alternative dosage regimen. In the present study, we have compared the pharmacokinetics in 12 healthy volunteers, of a single dose of 3 g of amoxycillin with those of 1 g as single dose or combined with 1 g of probenecid. The combination resulted in an AUC twice as large as that achieved after 1 g of amoxycillin, and was slightly, but not significantly, larger than that after 3 g. However, amoxycillin concentrations above 0.12 mg/l were sustained for almost 14 h with the combination as compared to 10.4 hours following 3 g of amoxycillin only (p less than 0.001). Thus, the combination should be a convenient alternative in patients unable to tolerate a higher oral dose of amoxycillin, and in situations when an antibacterial effect of longer duration is desired.

Scandinavian Journal of Infectious Diseases, 1989

The absorption of ampicillin esters is reported to decrease when gastric acidity is inhibited bec... more The absorption of ampicillin esters is reported to decrease when gastric acidity is inhibited because of hydrolysis of the esters, or by lowered solubility at a higher pH. No such information on the hydroxylated derivative amoxycillin is available. This was investigated in 8 fasting volunteers, who received 800 mg bacampicillin or 1000 mg amoxycillin on 4 study days, separated by at least 1 week. Each ampicillin derivative was administered on 1 occasion as a single drug, and on another after 1 week's pretreatment with the potent acid inhibitor omeprazole. Bacampicillin was absorbed more rapidly than amoxycillin, and serum peak concentrations were higher. After induced hypoacidity, peak concentrations of both antibiotics appeared to be slightly delayed, and those of bacampicillin significantly reduced. Nevertheless, both the areas under the plasma concentration curves, and the half lives of elimination of the antibiotics were unaffected. Hypoacidity as such does not reduce the bioavailability of amoxycillin or bacampicillin.

Scandinavian Journal of Infectious Diseases, 1997

A number of new antibiotics have lately become available for treatment of lower respiratory tract... more A number of new antibiotics have lately become available for treatment of lower respiratory tract infections in out-patients. The new drugs are generally more expensive than the older ones, which might be justified by better effects, improved safety, or by other advantages. In this study, a retrospective economic analysis has been made using data from a previous trial comparing a new macrolide, roxithromycin, with an older 1, erythromycin stearate in the treatment of lower respiratory tract infections. The trial was multicentre, double blind, randomized and comparative. There were no significant differences in efficacy between treatments, although the cure rate was higher for roxithromycin, 85% vs 79% for erythromycin. 20/39 of the erythromycin-treated patients reported adverse events, vs 7/40 roxithromycin-treated subjects, a highly significant difference. More detailed information was obtained by reviewing the medical records of the participants, and from questionnaires distributed to the 3 centres that had included patients in the trial. Additional visits were found necessary for 4 patients treated with erythromycin and for 1 using roxithromycin. Using the healing rates in the present investigation, and including costs for initial drug treatments, second consultations, and failed therapy, average cost-effectiveness (SEK/patient cured) was 409 for roxithromycin-treated patients, and 488 for erythromycin-treated. Roxithromycin should then be cheaper than erythromycin stearate. With the same healing rate, roxithromycin would be less cost-effective, but indirect costs and effects on quality of life are not then taken into account.

Scandinavian Journal of Infectious Diseases, 2003

Ever since dicloxacillin and cloxacillin were introduced in the 1960s, it has been known that the... more Ever since dicloxacillin and cloxacillin were introduced in the 1960s, it has been known that they are associated with a high incidence of infusion phlebitis. Some in vitro studies and clinical experience have indicated that dicloxacillin is the more vessel-irritating of the 2 drugs. In this prospective observational study on 39 patients with 111 peripheral venous catheters (PVCs), the incidence of infusion phlebitis was compared between these 2 drugs. The incidence of phlebitis was 38% with dicloxacillin and 21% with cloxacillin; which, compared by logistic regression with other risk factors as covariates, was significant [odds ratio 5.06, 95% confidence interval (95% CI) 1.45-17.60]. Since the duration of catheterization is also an important risk factor, Cox regression was performed, and the difference between the 2 drugs was still significant (proportional hazard rate 3.48, 95%, CI 1.64-7.38). The only other significant risk factor found in the study was the insertion site; the risk was higher in PVCs inserted in the forearm/antecubital fossa than in the hand/wrist. The infusion time and dilution of the infusate were not significant risk factors.

Journal of Infusion Nursing, 2004

This questionnaire study was set up to assess the perceptions of risk factors for infusion phlebi... more This questionnaire study was set up to assess the perceptions of risk factors for infusion phlebitis among Swedish nurses, as their concepts of these factors may influence the incidence. A majority of the nurses believed that insertion of a peripheral venous catheter in the forearm and catheter rotation within 48 hours was protective. These measures are not supported in recent studies and guidelines. Surveillance of the educational level of staff, who insert peripheral venous catheters, is an important tool for reducing the incidence of infusion phlebitis.

Pharmacology & Toxicology, 1987

The effect of intravenously administered ampicillin on plasma levels and renal clearance of enpro... more The effect of intravenously administered ampicillin on plasma levels and renal clearance of enprofylline was investigated in seven young and six elderly volunteers. On one occasion, each subject received 2 g of ampicillin intravenously, and serum concentrations of ampicillin were followed for 4 hours. On a separate occasion, a loading infusion of enprofylline was administered over 60 min., aiming at a plasma level of 2 micrograms/ml, and followed by a maintenance infusion. During this an infusion of 2 g of ampicillin was given for 10 min., and subsequently, renal clearance and plasma levels of enprofylline were followed for 4 hours. Plasma enprofylline levels increased significantly in the subjects after ampicillin infusion, but the effects on renal clearance of enprofylline were not statistically significant. The magnitude of the effects on enprofylline plasma levels and renal clearance from high doses of ampicillin do not suggest that interaction with beta-lactam antibiotics will be a serious problem for patients on enprofylline treatment.

Pharmacology & Toxicology, 1995

Intravenous administration of antibiotics often causes local pain and thrombophlebitis at the sit... more Intravenous administration of antibiotics often causes local pain and thrombophlebitis at the site of injection. An in vitro model that could predict these effects would be of great value. In this study the effects of four antibiotics, benzylpenicillin, cefuroxime, dicloxacillin and erythromycin, have been evaluated on three types of endothelial cells in culture. The cell types employed were primary culture from human umbilical vein, primary culture from bovine aorta, and the cell line EA-hy 926, a hybride endothelial cell. These cells were exposed to antibiotics for 24 hr and subsequently toxic effects on cells were evaluated by three different assays. Benzylpenicillin was atoxic in all types of cells and in all assays, in contrast to the other antibiotics. The other three antibiotics exerted dose dependent toxic effects in all investigated cells when DNA-synthesis and total cell protein were used as toxicity assays but the results varied between the cell types. There were no significant differences between the effects of cefuroxime, dicloxacillin and erythromycin on bovine endothelial cells. In the other cell types, however, there were significant differences between some drugs but the outcome depended on the cell type. It is concluded that it is possible to show differences between the effect of antibiotics on endothelial cells, but the result depends on the cell type employed.

Pharmacology & Toxicology, 2008

The irritating effect of parenterally administered antibiotics on vessels is a common clinical pr... more The irritating effect of parenterally administered antibiotics on vessels is a common clinical problem. In a previous study we found that solutions of three commonly used antibiotics, cefuroxime, erythromycin and dicloxacillin, exerted cytotoxic effects on endothelial cells after 24 hr exposure. In contrast benzylpenicillin did not have such effects. In the present study, endothelial cells of different origin were exposed to these four antibiotics at higher concentrations than in the previous investigation but only for 5, 30 and 60 min. Incorporation of 3 H-thymidine in the cells as a measurement of DNA synthesis was used as cytotoxic assay. A concentration-dependent and time-related inhibition was found after exposure to erythromycin and dicloxacillin but not after exposure to cefuroxime and benzylpenicillin. The effects were similar on the three different cell types used in the experiments. This study demonstrates that the cytotoxic effects differ even after short-term exposure to the antibiotics. In contrast to the previous study, cefuroxime lacks cytotoxicity when endothelial cells are exposed for less than one hour. The short-term exposition model used in this study should be more predictive as it mimics in vivo conditions better.

Archives Of Physiology And Biochemistry, 1985

The cure rate of acute uncomplicated urinary tract infection in general practice using 3 differen... more The cure rate of acute uncomplicated urinary tract infection in general practice using 3 different treatment regimens, was studied in a randomized, multicenter trial. Patients were assigned to receive either cefadroxil 1 g once daily for 3 or 7 days or amoxycillin 375 mg t.i.d. for 7 days. 310 patients entered the study, of whom 230 could be evaluated according to the protocol. Two thirds of the cases were due to infections with Escherichia coli and about one fourth to Staphylococcus saprophyticus. No statistically significant differences in cure rates between the 3 regimens could be demonstrated neither at 1 week nor at 5 weeks of follow-up. The frequency of adverse reactions was low and similar in each treatment group.