Paul Souney - Academia.edu (original) (raw)

Papers by Paul Souney

The Journal of laboratory and clinical medicine, 1983

We investigated the effects of varying salt intake on five factors that could affect sodium balan... more We investigated the effects of varying salt intake on five factors that could affect sodium balance during furosemide (F) administration: the quantity of F reaching the renal tubules; the magnitude of the acute natriuresis; Na+ excretion in the period after the acute diuresis; diuretic tolerance; and changes in plasma aldosterone. Six normal subjects were given F (40 mg day-1) for 3 days after equilibration to Na+ intakes of 20 mmol day-1 (low salt, LS) and 270 mmol day-1 (high salt, HS). Salt intake did not modify F excretion. Salt restriction reduced the short-term natriuretic response to F, led to diuretic tolerance, and potentiated the F-induced rise in plasma aldosterone. There was a progressive diminution in the quantity of Na+ excreted per unit of F excreted during LS. In spite of this, cumulative Na+ balance was negative only during LS because of a compensatory increase in Na+ reabsorption in the period between diuretic doses. During HS, this compensation exactly matched the...

Dicp-The annals of pharmacotherapy, Sep 1, 1979

Clinical Infectious Diseases, 1982

Single-dose antimicrobial therapy for uncomplicated urinary tract inductions in women has been re... more Single-dose antimicrobial therapy for uncomplicated urinary tract inductions in women has been reported and evaluated by several investigators. A review of the results of these studies suggest that amoxicillin, sulfisoxazole, and trimethoprim-sulfamethoxazole are effective single-dose regimens in this setting. These results should not be extrapolated to other populations, such as pregnant women or children, or to other antimicrobial agents. The limited data available suggest that cephalosporins are less effective than the regimens recommended. When the infecting organism is sensitive, failure to eradicate bacteriuria with one of these single-dose regimens may be indicative of a more invasive infection, perhaps in the kidney.

Gastroenterology, Aug 1, 1992

Vasoactive intestinal polypeptide (VIP) is one of the main neurotransmitters implicated in the re... more Vasoactive intestinal polypeptide (VIP) is one of the main neurotransmitters implicated in the relaxation of the lower esophageal sphincter (LES). The effect of exogenous VIP on LES motor activity was determined by esophageal manometry. LES pressure (LESP) and LES relaxation were compared in four healthy volunteers and in six patients with achalasia. The effects of intravenous doses of 1.5, 3, and 5 pmol.kg-1.min-1 of VIP were compared with placebo. Neither placebo nor 3 and 5 pmol.kg-1.min-1 of VIP produced any effect on esophageal motility in healthy volunteers. In achalasia the three doses of VIP caused a dose-dependent decrease in LESP with a significant improvement in LES relaxation. A dose of 5 pmol.kg-1.min-1 produced a maximal decrease of 51% in LESP. A beta-adrenergic agonist, isoproterenol, caused a decrease in LESP both in healthy volunteers and in patients with achalasia without improving LES relaxation. In summary, intravenous VIP improved LES relaxation and caused a decrease in LESP in patients with achalasia without affecting LESP in healthy volunteers, indicating that the LES muscle in achalasia is supersensitive to VIP. The current study suggests that a selective damage in the noncholinergic nonadrenergic innervation of the esophagus is in part responsible for the motor alteration seen in these patients. The findings and the inability of isoproterenol to improve LES relaxation despite decreasing LESP support a role in VIP as a indicator of LES relaxation.

American Journal of Health-system Pharmacy, Oct 1, 1987

American Journal of Health-system Pharmacy, Jul 1, 1988

American Journal of Health-system Pharmacy, Feb 1, 1984

Annals of Pharmacotherapy, May 1, 1993

To compareDialogEMBASEwith the National Library of Medicine's (NLM's) MEDLARS MEDLINE, TOXLINE,an... more To compareDialogEMBASEwith the National Library of Medicine's (NLM's) MEDLARS MEDLINE, TOXLINE,and TOXLITto evaluatedifferences among the databases and vendors in a methodconsistent with routinedrug information practice. DESIGN: Crossovercomparison. METHODS: NLM MEDLARS databases MEDLINE, TOXLINE,and TOXLITwere searcheddirectly. EMBASEwas searchedvia DialogInformation Services. MEDLINEwas searchedback to 1980; TOXLINEand TOXLIT were searched back to 1981, reflecting the different databasestructures. EMBASEwas searched back to 1980. To controlbias, searcheswere randomized; identical strategies were used duringthe same sessionand were performed by the same trainedsearcher. RESULTS: Twenty-six drug information requests were compared. The MEDLARS and Dialogdatabases were generally similar, with no significant differences in the numberof potentially relevant references, Englishreferences, clinically relevantreferences, available abstracts, uniquecitations, time online,and numberof questions answered. EMBASEsearcheswere morecostly (p=O.OOO5). TOXLIT was costlierthanTOXLINEand MEDLINE (p=O.OOI8). CONCLUSIONS: NLM MEDLARSdatabases were comparable to DialogEMBASE. AlthoughMEDLARS providedmore total and English-language citations, the differences were small and did not influence the proportion of questions answered. The greatest difference betweenthe vendorswas the significantly lowercost of searching on MEDLARS. Althoughthis difference may be partially offsetby the significantly shortersearchtimes on EMBASE,the mean 1.9minutessaved wouldnot recoupthe mean $7.89 difference in cost. MEDLARS databases are less expensive for routinedrug information requests.

Pharmacotherapy, Sep 10, 1988

Nicotinic acid (niacin) is a water-soluble vitamin widely used for the treatment of lipid disorde... more Nicotinic acid (niacin) is a water-soluble vitamin widely used for the treatment of lipid disorders. In pharmacologic doses (1 g or more/day), alone or in combination with other lipid-lowering drugs, nicotinic acid lowers very low-density (VLDL) and low-density lipoprotein (LDL) levels, while concurrently increasing high-density lipoprotein (HDL) levels. It may reduce long-term mortality in patients with known coronary artery disease and may slow or reverse the progression of atherosclerosis. A major consideration against using nicotinic acid is the occurrence of frequent, bothersome, adverse reactions such as cutaneous flushing, skin rash, and gastric upset. Careful dosing titration may, however, minimize these effects. The beneficial effects, taken together with the low cost of nicotinic acid therapy and the relative freedom from serious side effects, have made nicotinic acid the agent of choice for the treatment of many patients with hyperlipidemia.

Kidney International, Aug 1, 1983

Response of the kidney to furosemide. II. Effect of captopril on sodium balance. We investigated ... more Response of the kidney to furosemide. II. Effect of captopril on sodium balance. We investigated the role of the renin-angiotensin-aldosterone (RAA) system during furosemide (F) administration. The effects of adding captopril (C) (25 mg 6 hr') to F (40 mg daily for 3 days) were studied in six normal subjects equilibrated to a daily sodium (Na) intake of 270 mmoles. Without C, F produced a marked natriuresis but Na+ excretion fell sharply between drug doses. This resulted in neutral Na balance (+22 58 mmoles .3 days': mean SE). Plasma angiotensin (All) and aldosterone (Aldo) rose, but mean blood pressure (MBP) was unaltered. C abolished the F-induced increases in All and Aldo but did not modify the pattern of Na+ excretion. Na+ balance remained neutral (+42 54 mmoles 3 days'). With C alone, Na+ balance was positive (+ 110 30 mmoles .3 days1; P <0.02). In protocols C alone and F + C, MBP fell by a comparable amount. F alone and F + C increased plasma norepinephrine and prostaglandin E2 metabolite; these did not change with C alone. In conclusion, activation of the RAA system by F is not essential for the compensatory increase in Na+ reabsorption that maintains Na+ balance after F. Sympathetic nervous system activation or changes in prostaglandin E2 release may contribute to the increased Na+ reabsorption that follows the acute natriuresis induced by F. Rponse du rein au furosémide. II. Effet du captopril sur le bilan du sodium. Nous avons étudié le role du système rénine-angiotensinealdostérone (RAA) pendant l'administration de furosémide (F). Les effets de l'adjonction de captopril (C) (25 mg 6 hr') a F(40 mg par jour pendant 3 jours) ont été étudiés chez six sujets normaux equilibres avec un apport sodé (Na)journalier de 270 mmoles. Sans C, F a entrainé une natriurèse marquee mais l'excrétion de Na+ s'est effondrée entre les administrations du médicament. Cela a entraine un bilan de Na nul (-I-22

Dicp-The annals of pharmacotherapy, Oct 1, 1988

A 36-year-old woman was admitted for initiation of hemodialysis for chronic renal failure. Two da... more A 36-year-old woman was admitted for initiation of hemodialysis for chronic renal failure. Two days after catheter placement the patient developed a fever that persisted and resulted in subsequent removal of the catheter. Although blood cultures were negative, cultures of the catheter tip were positive for Staphylococcus epidermidis. An initial vancomycin dose was well tolerated, but the patient later experienced numbness and tingling of her lower back accompanied by pain ten minutes after initiation of the second dose. Symptoms abated when the vancomycin infusion was discontinued, and the drug was subsequently well tolerated when reinstituted at a slower infusion rate. Similar symptoms were observed five minutes into a vancomycin infusion a week later that also resolved after decreasing the infusion rate. Patients on hemodialysis receiving vancomycin should be carefully monitored during drug administration for the development of paresthesia and spasmodic lower back pain.

PubMed, 1993

Lidocaine-induced seizures have been reported after topical administration. A 30-year-old, 48-kg ... more Lidocaine-induced seizures have been reported after topical administration. A 30-year-old, 48-kg women with acquired immunodeficiency syndrome, chronic end-stage renal failure, anemia, congestive heart failure (CHF), cardiomyopathy, and increased liver function tests was admitted to the hospital with fever, chills, and dry cough. Bronchoscopy was performed to rule out Pneumocystis carinii pneumonitis; the patient experienced seizure activity after administration of a total dose of topical lidocaine 300 mg. Plasma drug concentration measured shortly after seizure, and at 4 and 22 hours after seizure were 12.0, 7.6, and 1.4 mg/L, respectively. A direct correlation exists between clinical symptoms and blood level of lidocaine; as the level increases to 8-12 mg/L the probability of seizure increases. The extent of absorption and bioavailability after airway administration depends on tissue vascularity, sites and techniques of application, patient's disease state, and, most important, the dose/unit body weight. The lidocaine dose should be titrated slowly and patients monitored for altered mental status. The dose often has to be decreased empirically in patients with liver disease or CHF. Efforts should be made to deliver minimum amounts of the drug to the lower respiratory tract, since its pharmacokinetics at that site are similar to those with intravenous administration.

Annals of Pharmacotherapy, May 1, 1996

To study the effects of ofloxacin on the reliability of urine glucose testing. DFSIGN: Open-label... more To study the effects of ofloxacin on the reliability of urine glucose testing. DFSIGN: Open-label, nonrandomized. SETIlNG: A university-affiliated tertiary care hospital, ambulatory clinic. PARTICIPANTS: Ten healthy volunteers (8 men and 2 women) aged 22-39 years. MAIN OUTCOME MEASURES: Phase I (in vitro) involved the addition of selected amounts of ofloxacin to a set of standard 50-mL urine samples prepared to simulate glycosuria. Phase II (in vivo) involved the oral administration of ofloxacin 400 mg to 10 subjects. Urine was collected: (I) immediately predose, (2) pooled 0-4 hours postdose, and (3) pooled 4-8 hours postdose. Known glucose concentrations were then added to these samples. Clinitest and Diastix tests were performed on all samples. The accuracy of these tests in determining glucose concentrations was compared among urine samples taken before and after ofloxacin dosing. RFSULTS: None of the ofloxacin concentrations in phase I (0, 25, 50, 100,200,400, and 800 IJg/mL) influenced these testing methods at the urine glucose concentrations of 0.0%, 0.5%, I%, and 2%. Likewise, the accuracy of these two tests was unaffected by ofloxacin administration in phase II.

The American Journal of Gastroenterology, Mar 1, 1999

Ortiz JE, Sottile FD, Sigel P, et al. Gastric Colonization as a Consequence of Stress Ulcer Proph... more Ortiz JE, Sottile FD, Sigel P, et al. Gastric Colonization as a Consequence of Stress Ulcer Prophylaxis: A Prospective, Randomized Trial Pharmacotherapy 1998;18:486–91

American Journal of Health-system Pharmacy, Jun 1, 1987

The Journal of Clinical Pharmacology, Feb 1, 2012

Intravenous amiodarone is an effective agent for the treatment of recurrent ventricular fibrillat... more Intravenous amiodarone is an effective agent for the treatment of recurrent ventricular fibrillation and hemodynamically unstable ventricular tachycardia. PM101 Premixed Injection is a new formulation of intravenous amiodarone that uses a cyclodextrin to maintain amiodarone in the aqueous phase. Eighty-eight subjects were enrolled in this randomized, single-blind, crossover, bioequivalence clinical study and were treated with single doses (150 mg) of PM101 Premixed Injection and intravenous amiodarone separated by a washout period of at least 42 days. Venous blood samples were taken periodically during the first 72 hours after dosing to determine standard pharmacokinetic parameters. The geometric ratio of the area under the concentration-time curve for time 0-72 hours (AUC 0-72hr) for amiodarone was 0.96 (95% confidence interval [CI], 0.94-0.99). The geometric ratio of the maximum concentration (C max) for amiodarone was 0.87 (95% CI, 0.84-0.91). Because these ratios and their CI fell between the limits of 0.8 and 1.25, bioequivalence of these 2 formulations was established. No safety concerns unique to the PM101 Premixed Injection, ready-to-use formulation were identified.

Clinical and Experimental Pharmacology and Physiology, Dec 27, 2011

1. PM103 is an intravenous formulation of clopidogrel being developed as an alternative to oral c... more 1. PM103 is an intravenous formulation of clopidogrel being developed as an alternative to oral clopidogrel to provide for dosing flexibility in the emergent clinical setting. The present first-inhuman study assessed the pharmacokinetic and pharmacodynamic effects of PM103 and its safety in 144 healthy human subjects. 2. The present was a randomized open-label parallel-group trial. Single intravenous doses of PM103 (0.1, 1.0, 10, 30, 100 or 300 mg) were administered to each group (n = 24 subjects per group). Platelet aggregation was assessed at baseline and then 15 and 30 min and 2, 5 and 24 h after drug administration. Determination of plasma concentrations of clopidogrel, clopidogrel carboxylic acid metabolite and the clopidogrel thiol metabolite were assessed at baseline and at 1, 5, 10, 20 and 30 min and 1, 2, 3, 4, 6, 8, 12 and 24 h after drug administration. 3. PM103 produced a rapid, persistent and dose-related inhibition of platelet aggregation. The onset of the ant platelet effect paralleled the appearance in plasma of the clopidogrel thiol active metabolite. PM103 was well tolerated and no subjects discontinued treatment because of adverse events. 4. These data suggest that PM103 may be a suitable alternative to oral clopidogrel for patients in whom the desired clinical management would include administration of clopidogrel after coronary angiography but prior to percutaneous coronary intervention.

Journal of Pharmaceutical and Biomedical Analysis, Nov 1, 1995

A simple, rapid, and sensitive fluorimetric-high-performance liquid chromatographic method for th... more A simple, rapid, and sensitive fluorimetric-high-performance liquid chromatographic method for the determination of propranolol in human serum/plasma has been developed, without the need for solvent extraction. The procedure required 200 microliters of serum/plasma, and the addition of 1 ml of acetonitrile for protein precipitation followed by vortexing and centrifugation at 10 000 g. The clear supernatant was evaporated to dryness under a stream of nitrogen at 50-60 degrees C, the residue was reconstituted in 100 microliters of methanol, and a 90 microliters portion was injected onto the high-performance liquid chromatograph for propranolol quantitation. Chromatography was accomplished using a Hypersil cyano column, a mobile phase of acetonitrile-aqueous acetic acid (1%) containing 0.2% triethylamine (35:65, v/v) (pH 3.6), a flow rate of 1.5 ml min-1, a fluorescence detector set at an excitation wavelength of 230 nm and an emission wavelength of 340 nm, and using pronethalol as the internal standard. Retention times for pronethalol and propranolol were 7.5 min and 9.5 min, respectively. Standard curves were linear in the range 5-200 ng ml-1. Relative standard deviations for both inter-day and intra-day precision analysis were less than 7% for serum. No interference was observed from endogenous serum/plasma components. Specificity was shown for some, but not all, commonly coadministered drugs tested. The advantages of this method include good precision, low sample volume, good reproducibility and recovery, and high sensitivity.

The American Journal of Gastroenterology, Mar 1, 2002

This prospective trial evaluated whether CYP2C19 genotype status was related to eradication rates... more This prospective trial evaluated whether CYP2C19 genotype status was related to eradication rates of Helicobacter pylori using triple therapy with a proton pump inhibitor, clarithromycin, and amoxicillin with an attempt to establish a strategy for treating patients whose H. pylori was not eradicated. Study patients consisted of men and women with endoscopically proven gastric ulcers or duodenal ulcers or long-standing gastritis who were positive for H. pylori using a rapid urease test, culture, and histology. The drug regimen for eradication of H. pylori included 20 mg of omeprazole or 30 mg of lansoprazole b.i.d. (randomly selected for proton pump inhibitor use), 200 mg of clarithromycin t.i.d., and 500 mg of amoxicillin t.i.d. for 1 wk. Patients with gastric or duodenal ulcer were treated with a daily dose of 20 mg of omeprazole or 30 mg of lansoprazole for 5–7 wk after triple therapy. Patients whose H. pylori was not eradicated with the initial regimen were retreated with 30 mg of lansoprazole q.i.d. and amoxicillin q.i.d. for 2 wk. Patients received endoscopic evaluation and confirmation of H. pylori status before treatment and 1 month after the end of all treatments. Endoscopic biopsy samples were obtained for rapid urease testing, bacteriological culture for antimicrobial sensitivity, and polymerase chain reaction analysis for genotyping of CYP2C19 status of patients. Patients were categorized into three groups based upon CYP2C19 genotype: homozygous extensive metabolizers, heterozygous extensive metabolizers, and poor metabolizers. There were no significant differences between the groups in demographic or disease state measures. Overall, 226 of 261 patients (86.6%) achieved cure of H. pylori infection. Thirty-three of 261 patients were infected with clarithromycin-resistant strains, whereas culture results revealed no amoxicillin-resistant strains. Differences in the status of CYP2C19 genotype and clarithromycin-resistant H. pylori were significantly associated with success or failure of H. pylori eradication. Eradication rates were 72.7% for homozygous extensive metabolizers, 92.1% for heterozygous metabolizers, and 97.8% for poor metabolizers. Thirty-four of 35 patients who did not achieve H. pylori eradication were classified as extensive metabolizers. Thirty-two of these patients were retreated, achieving H. pylori eradication.