Selim Kortunay - Academia.edu (original) (raw)

Papers by Selim Kortunay

group (23%) compared to that of the alcohol-dependents (42%, p ! 0.0001). We obtained no statisti... more group (23%) compared to that of the alcohol-dependents (42%, p ! 0.0001). We obtained no statistically significant difference among the ADH1C genotype groups regarding age. Conclusions: These findings suggest that a significantly higher presence of ADH1C * 2 allele is associated with alcohol dependence in a Turkish population. Studies with other related polymorphisms are needed to more precisely estimate the association of alcohol dependence with ADH1C .

International Journal of Pharmaceutics

Purpose: This study aimed to investigate the penetration of topical and oral ofloxacin into aqueo... more Purpose: This study aimed to investigate the penetration of topical and oral ofloxacin into aqueous humor and vitreous humor in post-traumatic endophthalmitis model in rabbits. Methods: A standardized intraocular infection after penetrating injury was made in the right eyes of 16 rabbits. Intraocular infection was induced by intravitreal injection of a suspension of Staphylococcus aureus. The intact left eyes were maintained as controls. The animals were divided randomly into two groups. (1) In the topical group, two drops of ofloxacin 0.3% eyedrops were instilled to both eyes every 30 min for 4 h. (2) In the topical-oral group, two doses of 25 mg/kg of ofloxacin at 12-h intervals were given orally, then the protocol of the first group was applied. Aqueous and vitreous humor samples were taken 30 min after the last drop. Ofloxacin concentrations were measured by using HPLC. Results: Mean aqueous levels of ofloxacin in control eyes were: 3.25±2.55 μg/ml in topical group, 4.58±5.39 μg...

The CLAO journal: official publication of the Contact Lens Association of Ophthalmologists, Inc

To assess the penetration of topical ciprofloxacin by a presoaked medicated disposable soft conta... more To assess the penetration of topical ciprofloxacin by a presoaked medicated disposable soft contact lens without topical drop administration. Disposable soft contact lenses were presoaked in 0.3% topical ciprofloxacin (Ciloxan, Alcon Laboratories, Fort Worth,TX) for 10-12 hours. Presoaked lenses were placed on the eyes of patients with senile cataracts for 3 hours in group A, 5-6 hours in group B, and 8-12 hours in group C prior to their scheduled lens extraction surgery. Aqueous humor samples were drawn by paracentesis during the operation. Ciprofloxacin concentrations were determined by high pressure liquid chromatography-fluorescence detection. The mean ciprofloxacin concentration was 2.70 +/- 0.98 microg/mL in group A, 1.22 +/- 1.0 microg/mL in group B, and 0.5 +/- 0.2 microg/mL in group C. Penetration of topical ciprofloxacin is enhanced through a presoaked disposable soft contact lens, and at 3 hours therapeutic levels are obtained. Significant levels of ciprofloxacin are reta...

Acta medica (Hradec Králové) / Universitas Carolina, Facultas Medica Hradec Králové

The effects of nonsteroidal antiinflammatory drugs, acetylsalicylate and metamizol, on spinal mon... more The effects of nonsteroidal antiinflammatory drugs, acetylsalicylate and metamizol, on spinal monosynaptic reflexes were investigated in spinalized and normal rats. Adult rats (n=36) weighing 150-200 g were anesthetized with ketamine and artificially ventilated. Half of rats were spinalized at C1 level. A laminectomy was performed in the lumbosacral region. Following electrical stimulation of the sciatic nerve by single pulses, reflex potentials were recorded from the ipsilateral L5 ventral root. Acetylsalicylate was administered orally (100 mg/kg for both spinalized and normal rats). Metamizol was administered intramuscularly (15 mg/kg for both spinalized and normal rats). These drug administrations significantly decreased the amplitude of reflex response in all groups (p < 0.05). These data verify that observed inhibition by acetylsalicylicate and metamizol may be at the level of spinal cord. Also we suggested that the cyclooxygenase products of arachidonic acid may play an imp...

Iranian Red Crescent Medical Journal, 2015

The treatment of cocaine toxicity is an important subject for emergency physicians. We investigat... more The treatment of cocaine toxicity is an important subject for emergency physicians. We investigated the effects of dexmedetomidine, moxonidine and alpha-methyldopa on acute cocaine toxicity in mice. The aim of this study was to evaluate the effects of dexmedetomidine, moxonidine and alpha-methyldopa in a mouse model of acute cocaine toxicity. We performed an experiment consisting of four groups (n = 25 each). The first group received normal saline solution, the second group received 40 µg/kg of dexmedetomidine, the third group received 0.1 mg/kg of moxonidine and the fourth group received 200 mg/kg of alpha-methyldopa, all of which were intraperitoneally administered 10 minutes before cocaine hydrochloride (105 mg/kg). All animals were observed for seizures (popcorn jumping, tonic-clonic activity, or a loss of the righting reflex) and lethality over the 30 minutes following cocaine treatment. The ratio of animals with convulsions was lower in all treated groups when compared to the control (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Furthermore, 68% (n = 17) of animals in the dexmedetomidine group, 84% (n = 21) of the alpha-methyldopa group, 92% (n = 23) of the moxonidine group and 100% (n = 25) of the control group showed evidence of seizure activity (P = 0.009). Cocaine-induced lethality was observed in 12% (n = 3) of the dexmedetomidine group, 48% (n = 12) of the alpha-methyldopa group, 52% (n = 13) of the moxonidine group, and 72% (n = 18) of the control group (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). All treatments prolonged the time to seizure, which was longest in the dexmedetomidine group (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 0.05). In addition, the time to lethality was also longer in the same group (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). The present study provides the first experimental evidence in support of dexmedetomidine treatment for cocaine-induced seizures. Premedication with dexmedetomidine reduces seizure activity in a mouse model of acute cocaine toxicity. In addition, while dexmedetomidine may be effective, moxonidine and alpha-methyldopa did not effectively prevent cocaine-induced lethality.

Clinical pharmacology and therapeutics, 1999

The genetically polymorphic cytochrome P450 enzymes 2Cl9 (CYP2Cl9) and 2D6 (CYP2D6) contribute to... more The genetically polymorphic cytochrome P450 enzymes 2Cl9 (CYP2Cl9) and 2D6 (CYP2D6) contribute to the metabolism of about 30% of all drugs. For analysis of the ethnic-related differences in drug disposition and as a preparation for routine genotyping, we examined CYP2C19 and CYP2D6 mutations in a large Turkish population. CYP2C19 and CYP2D6 alleles were determined with use of genomic deoxyribonucleic acid from 404 unrelated Turkish individuals. CYP2C19 alleles *1 to *5 and CYP2D6 alleles *1 to *12, and *14, *15, and *17 were measured by polymerase chain reaction-restriction fragment length polymorphism assays. From 404 subjects genotyped for CYP2C19, allele frequencies of CYP2C19*1 (wt), CYP2C19*2 (ml), and CYP2C19*3 (m2) were 0.88, 0.12, and 0.004, respectively; mutations m3 and m4 were not found. Four individuals (1.0%) were predicted to be poor metabolizers (CYP2C19*2/*2), a significantly lower frequency compared to Middle European populations. Among 404 subjects genotyped for CY...

International Journal of Pharmaceutics, 2000

To study the aqueous and vitreous penetration of ciprofloxacin after prolonged acute topical admi... more To study the aqueous and vitreous penetration of ciprofloxacin after prolonged acute topical administration and to investigate the effects of inflammation on drug penetration. A standardized model of intraocular infection after penetrating injury was made in the right eyes of eight rabbits. The intact left eyes were maintained as the control. Two drops of ciprofloxacin 0.3% eyedrops were instilled topically every 1 h for 7 h to all eyes of the rabbits. Aqueous and vitreous samples (100 microl) were obtained half an hour after the last drop. Instillation was continued for 7 h more and samples were obtained as before. Drug concentrations were measured using HPLC. The mean aqueous humor levels of ciprofloxacin were: in control eyes 1.31 +/- 0.78 microg/ml after 7 h and 1.85 +/- 1.69 microg/ml after 14 h of instillation: in inflamed eyes 2.18 +/- 1.02 microg/ml after 7 h and 2.91 +/- 2.12 microg/ml after 14 h. The mean vitreous humor levels were: in control eyes 0.65 +/- 0.44 microg/ml after 7 h and 0.72 +/- 0.8 microg/ml after 14 h of instillation; in inflamed eyes 0.67 +/- 0.77 microg/ml after 7 h and 1.01 +/- 0.43 microg/ml after 14 h. However, the differences among the groups were not significant (P > 0.05). Ciprofloxacin penetration into aqueous humor was higher in 14-h topical application than that for 7 h. Inflammation increased the penetration of topical ciprofloxacin into aqueous while administered for 7 h and into both aqueous and vitreous humor while administered for 14 h. c

Retina, 1999

This study was designed to determine the effects of trauma and infection on vitreous ciprofloxaci... more This study was designed to determine the effects of trauma and infection on vitreous ciprofloxacin levels after intravitreal injection of ciprofloxacin in rabbits. A penetrating injury was made in the right eyes of 24 rabbits. In the eyes of half of the traumatized animals, a standardized intraocular infection was induced by intravitreal injection of a suspension of Staphylococcus aureus. The intact left eyes of the traumatized group were maintained as controls. Ciprofloxacin (200 microg/0.1 mL) was injected into the midvitreous cavity of both eyes in all animals and samples were obtained at 2, 8, 24, and 48 hours after injection. Drug concentrations were measured using high-pressure liquid chromatography analysis. At the second hour, the mean vitreous concentration of ciprofloxacin in the traumatized eyes was lower than that in control eyes (P<0.05). The mean ciprofloxacin concentrations were significantly higher (P<0.05) in the traumatized-infected eyes than were those in control or traumatized eyes at 24 and 48 hours. The elimination half-life of ciprofloxacin in control and traumatized eyes was 6.02 hours and 5.02 hours, respectively, and infection prolonged the half-life to 15.06 hours. Vitreous levels of ciprofloxacin were above the minimum inhibitory concentration (MIC90) for most of the common microorganisms causing endophthalmitis in all groups at 2 and 8 hours, but also at 24 and 48 hours in traumatized-infected eyes. Infection appears to decrease the clearance of ciprofloxacin. Therapeutic drug levels in traumatized-infected eyes were maintained up to 48 hours. Assuming that the animal model used may have a predictive value for the drug elimination in traumatized-infected human eyes, we suggest that local administration of ciprofloxacin every 2 days may be relevant from the therapeutic perspective.

RETINA, 1999

To assess the aqueous and vitreous penetration of ciprofloxacin after topical and combined topica... more To assess the aqueous and vitreous penetration of ciprofloxacin after topical and combined topical and oral administration and investigate the effects of inflammation on drug penetration. A standardized penetrating injury was made in the right eyes of 16 rabbits. Intraocular inflammation was induced by intravitreal injection of a suspension of Staphylococcus aureus in these eyes. The animals were divided into two groups according to treatment methodology: topical and topical-oral. The intact left eyes of the animals were maintained as controls. In the topical treatment group, two drops of ciprofloxacin 0.3% were instilled to both eyes every 30 minutes for 4 hours. In the topical-oral treatment group, animals were given two oral 40 mg/kg doses of ciprofloxacin at 12-hour intervals. After the last oral dose, the protocol of the topical group was applied to these eyes. Half an hour after the last drop, 100-microL samples were taken from aqueous and vitreous humor of all eyes. Drug concentrations were measured using high-pressure liquid chromatography. Mean aqueous levels of ciprofloxacin in control eyes were 2.31 microg/mL (range, 1.02-6.27 microg/mL) in the topical group and 5.88 microg/mL (1.52-17.81) in the topical-oral group. Mean aqueous levels in inflamed eyes were 7.36 microg/mL (2.34-17.15) in the topical group and 14.43 microg/mL (2.18-18.66) in the topical-oral group. Mean vitreous levels in control eyes were 0.77 microg/mL (0.09-1.93) in the topical group and 1.01 microg/mL (0.49-1.57) in the topical-oral group. Mean vitreous levels in inflamed eyes were 0.95 microg/mL (0.18-1.27) in the topical group and 1.98 microg/mL (0.51-3.34) in the topical-oral group. There was no significant difference among the groups (P > 0.05). Mean aqueous levels in all eyes and mean vitreous levels in the combined topical and oral group of inflamed eyes were above the 90% minimum inhibitory concentration for most of the common microorganisms causing endophthalmitis. There is an increase in both aqueous and vitreous humor concentrations with inflammation and with oral and topical administrations, as opposed to topical only, of ciprofloxacin. Using oral as well as topical treatment may be a beneficial method of antibiotic prophylaxis in ocular trauma once a patient has received intravenous or intravitreal therapy.

Pharmacology, 2003

The effects of acetylsalicylate and metamizol on spinal monosynaptic reflexes were tested in spin... more The effects of acetylsalicylate and metamizol on spinal monosynaptic reflexes were tested in spinal rats. Adult rats were anesthetized with ketamine, artificially ventilated, and spinalized at the C1 level. A laminectomy was performed in the lumbosacral region. Following electrical stimulation of the sciatic nerve by single pulses, the reflex potentials were recorded from the ipsilateral L5 ventral root. Acetylsalicylate was administered orally via nasogastric tube and metamizol intramuscularly. Acetylsalicylate (50 and 100 mg/kg) and metamizol (15 mg/kg) significantly decreased the amplitude of the reflex response (p < 0.05). But the 10-mg/kg metamizol dose did not significantly decrease the amplitude of the reflex response. The cyclooxygenase products of arachidonic acid may play an important role in regulating the reflex potential.

Peptides, 2012

Orexins have been implicated in the regulation of sleep-awake cycle, energy homeostasis, drinking... more Orexins have been implicated in the regulation of sleep-awake cycle, energy homeostasis, drinking behavior, analgesia, attention, learning and memory but their effects on epileptic activity are controversial. We investigated whether intracortical injections of orexin A (100 pmol) and B (100 pmol) cause epileptic activity in rats. We observed epileptic seizure findings on these two groups rats. Orexin A and B also significantly increased total EEG power spectrum. Our findings indicate that orexins cause epileptic activity.

Ophthalmic Research, 1999

This study was carried out to get an insight into the ofloxacin elimination after intravitreal in... more This study was carried out to get an insight into the ofloxacin elimination after intravitreal injection in rabbits. We also studied the effects of trauma and inflammation on the vitreous ofloxacin levels after intravitreal injection of ofloxacin. A penetrating eye injury in the right eye was inflicted on 24 rabbits and another 12 animals were used as control. A standardized intraocular inflammation was induced by intravitreal injection of a suspension of Staphylococcus aureus in half of the traumatized eyes. Ofloxacin (200 microg/0.1 ml) was injected into the midvitreous cavity of both traumatized and control right eyes, and samples were obtained at 2, 8, 24 and 48 h after injection. Drug concentrations were measured using high-pressure liquid chromatography analysis. Vitreous levels of ofloxacin were above the MIC(90) at 2 and 8 h in all groups for most of the common microorganisms causing endophthalmitis and also at 24 h in traumatized-infected eyes. At the second hour, the mean vitreous concentrations of ofloxacin both in traumatized and traumatized-infected eyes were lower than that in the control eyes (p &amp;lt; 0.05). At 8 h, the mean vitreous concentrations of ofloxacin in the traumatized and in the traumatized-infected eyes were higher than that in the control eyes (p &amp;lt; 0.05). At 24 h, the mean ofloxacin concentration was higher in the traumatized-infected eyes than that in control (p &amp;lt; 0.01) and traumatized eyes (p &amp;lt; 0.05), and also higher in the traumatized eyes than that in the control eyes (p &amp;lt; 0.05). The mean ofloxacin concentrations in the traumatized and traumatized-infected eyes were significantly higher (p &amp;lt; 0.01) than those in the controls at 48 h. The elimination half-life of ofloxacin in the control eyes was 5.65 h and trauma and inflammation prolonged the half-life to 9.47 and 9. 72 h, respectively. Clearance of ofloxacin is fast and appears to be reduced by trauma and inflammation. Therapeutic drug levels in traumatized-infected eyes were maintained up to 24 h. This may be an important pharmacokinetic advantage in treating endophthalmitis unless the dose used has local toxicity and allows a longer dose interval when the dose is repeated.

Neurological Research, 2012

Objective: To evaluate the effects of etomidate, ketamine, phenytoin, and phenytoin/midazolam in ... more Objective: To evaluate the effects of etomidate, ketamine, phenytoin, and phenytoin/midazolam in a mouse model of acute cocaine toxicity. Methods: We performed a randomized controlled study consisting of five groups (n525 each) of rats that received intraperitoneal injections of normal saline solution, 5 mg/kg ketamine, 7.5 mg/kg etomidate, 40 mg/kg phenytoin, and 40 mg/kg phenytoin and 2 mg/kg midazolam 10 minutes before cocaine hydrochloride (105 mg/kg). Following cocaine administration, a blinded observer watched the animals for 30 minutes to assess seizures (popcorn jumping, tonic-clonic activity, or loss of righting reflex), and lethality for 30 minutes. Results: The number of animals with seizures was lower in the etomidate (60%), phenytoin (40%), and phenytoin/midazolam (40%) groups (P,0.001). The etomidate (24%) and phenytoin/midazolam (16%) treatments were most effective in preventing lethality (P,0.001). Conversely, compared to the vehicle group (72%), cocaine-induced lethality was higher in the ketamine (84%) and phenytoin (92%) groups. All treatments prolonged the time to seizure, but this effect was most pronounced in the etomidate and phenytoin/midazolam groups, which also had the longest average time to lethality. Discussion: The present study provides the first experimental evidence supporting the use of etomidate to treat cocaine-induced seizures. Notably, ketamine and phenytoin were ineffective. Our findings suggest that premedication with etomidate, phenytoin, and phenytoin/midazolam reduced seizure activity in an acute cocaine toxicity mouse model.

Methods and Findings in Experimental and Clinical Pharmacology, 2006

Alcohol dehydrogenase (ADH) is a genetically polymorphic dimeric enzyme that is responsible for t... more Alcohol dehydrogenase (ADH) is a genetically polymorphic dimeric enzyme that is responsible for the metabolism of alcohol. ADH3 gene encodes for the gamma subunit of dimeric ADH and has an important role in the function of the enzyme. The aim of this study was to determine the frequencies of ADH3 alleles and genotypes in a healthy Turkish population sample. Genotypic assay was carried out in 102 unrelated volunteers. DNA samples were genotyped for the ADH3*2 allele. The ADH3*1 and ADH3*2 allele frequencies were determined as 0.66 (95% confidence interval [CI] = 0.57-0.75) and 0.34 (95% CI = 0.25-0.43), respectively. The genotype frequencies of ADH3*1/*1, *1/*2, and *2/*2 were 39% (95% CI = 30-49), 54% (95% CI = 44-64), and 7% (95% CI = 2-12), respectively. According to our results, the frequencies of variant ADH3 alleles and genotypes are similar to that in the other Caucasian populations.

Methods and Findings in Experimental and Clinical Pharmacology, 2010

Squamous cell carcinoma of the head and neck (SCCHN) have been reported to be related to both gen... more Squamous cell carcinoma of the head and neck (SCCHN) have been reported to be related to both genetic and environmental factors, including alcohol consumption and alcohol-metabolizing enzymes such as alcohol dehydrogenase (ADH). We conducted a hospital-based, case-control study including 50 cases with diagnosed SCCHN and 100 controls with non-neoplastic conditions such as upper respiratory tract infection. The genomic DNA was isolated from peripheral blood leukocytes. The ADH1C*1 wild-type and ADH1C*2 variant alleles were analyzed with an RFLP method by using SspI as restriction enzyme. The ADH1C*1 allele frequencies were 0.89 (CI95% = 0.84-0.91) in controls and 0.77 (CI95% = 0.71-0.83) in cases, and respective frequencies of the ADH1C*2 allele were 0.11 (CI95% = 0.07-0.14) and 0.23 (CI95% = 0.17-0.29) among controls and cases (P = 0.01). The ADH1C*1/*1 genotype frequency was significantly higher in the control group (77%) compared to that of the cases (58%) (P = 0.02).These findings suggest that a lower presence of ADH1C*1 allele is associated with SCCHN, but larger numbers are needed to more precisely estimate the interaction, if any, with ADH1C. Interestingly, the ADH1C allele and genotype frequencies in our control group living in Denizli were significantly different compared to a previously published report from healthy volunteers living in Ankara (P < 0.0001).

European Journal of Drug Metabolism and Pharmacokinetics, 2002

The aim of this study was to investigate the effects of two antihistaminic drugs, terfenadine and... more The aim of this study was to investigate the effects of two antihistaminic drugs, terfenadine and diphenhydramine on CYP2D6 activity by using debrisoquine as a model substrate. The study was carried out as an in vivo single-dose study in 12 young, healthy men. All volunteers had previously been identified as debrisoquine-extensive metabolisers. The volunteers took increasing single oral doses of one of the two antihistaminic drugs in randomized order, at weeklyy intervals, followed I h later by debrisoquine test. Terfenadine and diphhenhydramine were given in the doses of 60 and 120 mg: 100 and 150 mg, respectively. The 8-hr urinary concentrations of debrisoquine and 4-hydroxydebrisoquine were determined by high-performance liquid chromatography (HPLC). With increasing doses of terfenadine and diphenhydramine, there was no statistically significant increase in the debrisoquine metabolic ratios (P> 0.05, Page's test for trend). The difference between the median debrisoquine metabolic ratios before and after treatments with terfenadine or diphenhydramine were not statistically significant (Wilcoxon's test). This investigation indicates that single-dose administration of diphenhydramine or terfenadine has no effect on the CYP2D6-mediated hydroxylation of debrisoquine in healthy volunteers.

European Journal of Clinical Pharmacology, 2001

Objectives: The objective of our study was to investigate the possible role of human arylamine N-... more Objectives: The objective of our study was to investigate the possible role of human arylamine N-acetyltransferase 2 (NAT2) polymorphism in susceptibility to BehcË et's disease. Methods: Eighty-®ve patients with BehcË et's disease gave their written informed consent to participate in the study. Seven point mutations (G191A, C282T, T341C, C481T, A803G, G590A, G857A) in the NAT2 gene were analysed using polymerase chain reaction/restriction fragment length polymorphism techniques. In addition, each patient received 100 mg dapsone orally to determine their NAT2 phenotype. Dapsone and its metabolite monoacetyl-dapsone were measured in 3-h plasma samples using high-performance liquid chromatography. Subjects with an acetylation ratio (monoacetyl-dapsone/ dapsone) less than 0.4 were de®ned as slow acetylators. Results: Of 85 patients with BehcË et's disease, 54 (63.5%) were identi®ed as genotypically slow acetylators. However, 60% (51 of 85) of patients were diagnosed as slow acetylators according to monoacetyl-dapsone/dapsone ratio. Thus, a low incidence of genotype/phenotype discrepancy (3.5%) was observed in Turkish patients with BehcË et's disease. When we compared our results with previous phenotyping and genotyping studies in the Turkish population, frequencies of slow and rapid acetylators were not statistically dierent in patients with BehcË et's disease. The frequency of the *5B allele was found to be slightly higher in patients with BehcË et's disease than historic controls (44.7 vs 35.6%, P=0.039). However, there was no signi®cant dierence in the frequency of the overall genotypes and alleles of NAT2 between patients and controls. Conclusion: Although the frequency of the NAT2*5B allele, responsible for slow acetylation, was slightly higher in patients than historic controls, our results failed to show an association between NAT2-acetylator status and risk for developing BehcË et's disease.

European Journal of Clinical Pharmacology, 1997

Objectives: This pharmacogenetic study was aimed at studying the pattern of oxidation of omeprazo... more Objectives: This pharmacogenetic study was aimed at studying the pattern of oxidation of omeprazole in a Turkish population and testing whether omeprazole metabolism cosegregates with the genetically determined metabolism of mephenytoin and proguanil in Turkish subjects. Methods: The hydroxylation of omeprazole was measured in 116 unrelated healthy Turkish subjects after administration of a single oral dose of omeprazole (20 mg), using the ratio of omeprazole to 5-hydroxyomeprazole in plasma 3 h after dosing. To 31 subjects, who were phenotyped with omeprazole, mephenytoin (100 mg, p.o.) or proguanil (200 mg, p.o.) were administered at least 1 week apart. The S/R ratio of mephenytoin and the ratio of proguanil to cycloguanil were determined from an 8-h urine collection. Results: Based on the distribution of the log (omeprazole/hydroxyomeprazole) values and using the antimode value of 0.8, the frequency of poor metabolizers of omeprazole was estimated to be 7.7% (95% con®dence interval 3±18%) which was similar to that in the other Caucasian populations (P = 0.54, Fisher's exact test). Three poor metabolizers of omeprazole were also clas-si®ed as poor metabolizers of both mephenytoin and proguanil and no misclassi®cation occurred with three phenotyping methods. All three methods separated poor or extensive metabolizer phenotypes with complete concordance. The ratio of omeprazole to hydroxyomeprazole correlated with the S/R ratio of mephenytoin and the ratio of proguanil to cycloguanil.

European Journal of Clinical Pharmacology, 1999

To determine whether patients with idiopathic systemic lupus erythematosus (SLE) are associated w... more To determine whether patients with idiopathic systemic lupus erythematosus (SLE) are associated with impaired CYP2D6 activity and to gain insight into whether there is an association between particular CYP2D6 genotypes and susceptibility to SLE, and whether CYP2D6 polymorphism is linked to any specific clinical features of SLE. Debrisoquine sulfate (10 mg p.o.) was given to 159 healthy volunteers and 39 idiopathic SLE patients. Genotypic assay was carried out in 80 healthy volunteers and 32 patients. A 10-ml blood sample was drawn for genotypic assay. Debrisoquine and 4-hydroxydebrisoquine were determined in 8-h urine samples. Blood samples were analysed for the presence of mutations in the CYP2D6 gene, by using polymerase chain reaction (PCR) specific for CYP2D6*3 and CYP2D6*4 alleles. The metabolic ratio of debrisoquine to 4-hydroxydebrisoquine ranged from 0.01 to 86.98 in healthy subjects and from 0.02 to 96 in SLE patients. We observed the poor metabolizer(PM) debrisoquine phenotype in three of 39 patients with idiopathic SLE (7.6%) and five of 159 healthy subjects (3.1%). There was no significant difference in the frequency of PM phenotypes between idiopathic SLE and healthy subjects (Fisher's exact test, P = 0.19). No significant difference in the distribution of overall genotypes and allele frequencies were observed between the two groups. No significant relationships were found between specific clinical features and the overall genotype. The results of this study confirm that CYP2D6 activity is not impaired in SLE and that there is no association between SLE and phenotypic CYP2D6 status. The results also showed that there was no difference in the frequency of CYP2D6A and CYP2D6B alleles between controls and patients with SLE.