Effects of Genetic Polymorphisms of Cytochrome P450 Enzymes and MDR1 Transporter on Pantoprazole Metabolism and Helicobacter pylori Eradication.

Pantoprazole is a proton pump inhibitor that is commonly used in the treatment of peptic ulcer disease (PUD) and metabolized by cytochrome P450 (CYP) enzymes CYP2C19 and CYP3A4. Pantoprazole is a substrate for multi-drug resistance protein 1 (MDR1). Single nucleotide polymorphisms (SNPs) in CYP2C19, CYP3A4 and MDR1 affect enzyme activity or gene expression of proteins and may alter plasma pantoprazole concentrations and treatment success in PUD. In this study, we aimed to investigate the association between genetic polymorphisms in CYP2C19, CYP3A4 and MDR1 and pharmacokinetics of pantoprazole and therapeutic outcome in patients with either Helicobacter pylori-associated [H.P.(+)]-PUD or [H.P.(+)]-gastritis. The plasma pantoprazole concentrations were determined by using an HPLC method at the third hour after a 40-mg tablet of pantoprazole administration in 194 newly diagnosed patients with either [H.P.(+)]-PUD or [H.P.(+)]-gastritis. Genotyping was performed by using PCR-RFLP and DNA sequencing. Among patients appearing for follow-up examination (n = 105), the eradication rate for H. pylori was 82.8% (n = 87). The median pantoprazole plasma concentrations in poor metabolizers (PM), rapid metabolizers (RM) and ultrarapid metabolizers (URM) were 2.07, 1.69 and 1.28 µg/ml, respectively (p = 0.04). CYP3A4*1G and *22 polymorphisms did not affect plasma pantoprazole concentrations and H. pylori eradication rate. The MDR1 genetic polymorphisms did not affect plasma pantoprazole concentrations. MDR1 3435CC-2677GG-1236CC haplotype carriers had lower H. pylori eradication rate (60%) than the remaining subjects (84.9%) while the difference was not statistically significant (p = 0.07). In conclusion, while CYP2C19 genetic polymorphisms significantly affected plasma pantoprazole concentrations, polymorphisms of CYP2C19, CYP3A4 and MDR1 did not affect H. pylori eradication rates.

Relation of the Allelic Variants of Multidrug Resistance Gene to Agranulocytosis Associated With Clozapine.

Clozapine use is associated with leukopenia and more rarely agranulocytosis, which may be lethal. The drug and its metabolites are proposed to interact with the multidrug resistance transporter (ABCB1/MDR1) gene product, P-glycoprotein (P-gp). Among various P-glycoprotein genetic polymorphisms, nucleotide changes in exons 26 (C3435T), 21 (G2677T), and 12 (C1236T) have been implicated for changes in pharmacokinetics and pharmacodynamics of many substrate drugs. In this study, we aimed to investigate the association between these specific ABCB1 polymorphisms and clozapine-associated agranulocytosis (CAA). Ten patients with a history of CAA and 91 control patients without a history of CAA, despite 10 years of continuous clozapine use, were included. Patient recruitment and blood sample collection were conducted at the Hacettepe University Faculty of Medicine, Department of Psychiatry, in collaboration with the members of the Schizophrenia and Other Psychotic Disorders Section of the Psychiatric Association of Turkey, working in various psychiatry clinics. After DNA extraction from peripheral blood lymphocytes, genotyping was performed using polymerase chain reaction and endonuclease digestion. Patients with CAA had shorter duration of clozapine use but did not show any significant difference in other clinical, sociodemographic characteristics and in genotypic or allelic distributions of ABCB1 variants and haplotypes compared with control patients. Among the 10 patients with CAA, none carried the ABCB1 all-variant haplotype (TT-TT-TT), whereas the frequency of this haplotype was approximately 12% among the controls. Larger sample size studies and thorough genetic analyses may reveal both genetic risk and protective factors for this serious adverse event.

Oral Candida carriage and prevalence of Candida species among Maras powder users and non-users.

INTRODUCTION: The aim of this study was to investigate Candida carriage and species in Maras powder users and non-users. MATERIAL AND METHODS: This study included 100 volunteering men in 12 cafés in the city of Kahramanmaras, Turkey. A questionnaire composed of questions about socio-demographic features and Maras powder use was filled in by the participants. Culture specimens were obtained from bilateral buccal mucosa and dorsum of the tongue with a sterile cotton-tipped swap. The specimens were inoculated in Sabouraud Dextrose Agar (SDA). RESULTS: The mean age of the participants was 48.0 ± 12.5 years (min = 20, max = 70). Fifty-four percent of the Maras powder users and 22% of the non-users were Candida carriers. The difference between the groups was significant (P = 0.001). The most frequently isolated species was Candida albicans at a rate of 44% in the Maras powder users and at a rate of 18% in the non-users. Other frequent species were Candida glabrata at a rate of 6% in the Maras powder users and 2% in the control group and Candida tropicalis at a rate of 4% in the Maras powder users and 2% in the nonusers. CONCLUSION: We found that a significantly high rate of the Maras powder users was Candida carriers. It should be kept in mind that opportunistic infections may be caused by Candida species in Maras powder users especially with immunosuppressive conditions since Candida species are likely to lead to such infections in cases of immunosuppressive diseases.

Ocular pharmacokinetics, safety and efficacy of intracameral moxifloxacin 0.5% solution in a rabbit model.

PURPOSE: This study was carried out to determine the ocular pharmacokinetics, efficacy and potential endothelial toxicity of moxifloxacin (MF) after a single intracameral bolus injection of 500 µg/0.1 ml in a rabbit model. MATERIALS AND METHODS: Forty-eight eyes of 24 New Zealand White Rabbits were separated into six groups, each including four rabbits. 0.1 ml of 0.5% intracameral moxifloxacin (500 µg) injection was injected to the right eyes and 0.1 ml of balanced salt solution to the left eyes (control). Aqueous humor (AH) and vitreous samples were collected at the 0.5th, 1st, 3rd, 6th, 12th and 24th hours from both eyes of group 1, 2, 3, 4, 5 and 6, respectively. MF concentrations were determined by high performance liquid chromatography. These were compared with the minimum inhibitory concentrations (MIC) and mutant prevention concentrations (MPC) for frequent endophthalmitis pathogens. Electron and light microscopical evaluation of the corneas were performed. RESULTS: Moxifloxacin reaches higher concentration than the MIC of all common endophthalmitis pathogens in the AH and exceeds the mutant prevention concentration levels for Streptococcus pneumonia, Streptococcus viridans, flouroquinolone susceptible Coagulase-negative staphylococcus and flouroquinolone susceptible Staphylococcus aureus for 6 h. The half-life of moxifloxacin in the AH was 2.2 h. Electron and light microscopic evaluation revealed no noticeable sign of toxicity. CONCLUSIONS: Peroperative intracameral moxifloxacin injection for endophthalmitis prophylaxis is a safe and effective method in uncomplicated phacoemulsification surgery.