ABCB1 polymorphism in clopidogrel-treated Montenegrin patients.

Clopidogrel is an antiplatelet drug that displays significant interindividual variability in treatment response. Its bioavailability depends on the function of P-glycoprotein (P-gp), which is coded by a highly polymorphic ABCB1 gene. Thus, the aim of this study was to investigate the effect of ABCB1 genetic polymorphism on clopidogrel efficacy and safety and to determine the frequency distribution of its most common single nucleotide polymorphisms (SNPs) in 106 Montenegrin cardiology patients. Clopidogrel efficacy and safety were followed up during 1 year after hospitalization, with the lack of efficacy and adverse drug reactions observed in 11 (10.4%) and 8 patients (7.5%), respectively. Genotyping for ABCB1 SNPs rs1128503 (1236C > T), rs2032582 (2677G > A/T), and rs1045642 (3435C > T) was performed by the real-time PCR method, and the variant alleles were detected with the frequencies of 42.9, 44.8, and 52.8%, respectively. No significant association was observed between any of the examined genotypes and clopidogrel efficacy (p = 0.253) or safety (p = 0.424). Due to small sample size, co-treatment with other drugs, and other genetic factors not taken into account, we believe the absence of correlation between ABCB1 genotypes and indicators of clopidogrel efficacy and safety in this study should be apprehended conditionally, and that larger and better-controlled studies are warranted.

Relationship between outpatient antibiotic use and the prevalence of bacterial infections in Montenegro.

Background/Aim: The overuse of antibiotics unnecessarily exposes patients to risk of side effects, encourages reconsultation for similar problems and enhances antimicrobial resistance. The use of antibiotics in the year 2011 in Montenegro was high (39.05 Defined Daily Dose ­ DDD/1,000 inhabitants/day), but it was not considered in relation to the frequency of bacterial diseases. The aim of our study was to determine the degree of conformance between the amount of outpatient antibiotic consumption and the reported prevalence of outpatient bacterial infections in the Republic of Montenegro. Methods: Data on the use of antibacterial drugs was obtained from the Agency for Medicines and Medical Devices of Montenegro for the year 2012. The amount of antibiotics was calculated using the Anatomic Therapeutic Chemical (ATC) DDD methodology. Data on the prevalence of outpatient infective disease was obtained from the Health Statistical Yearbook 2012 of Montenegro and it was expressed per 1,000 inhabitants. Results: A total of 30.34 DDD/1,000 inhabitants/day of antibiotics in outpatients were prescribed in Montenegro in 2012, with penicillins being most frequently prescribed. Amoxicillin and amoxicillin with clavulanic acid were the most frequently used antibiotics. The prevalence of outpatient bacterial infections was 6,745 cases or 10.87/1,000. The most frequent infections were respiratory tract infections. Less than 50% of the prescribed amount of antibiotics were prescribed in accordance with national guidelines on treatment of bacterial infections. Conclusion: Use of antibiotics in Montenegro in 2012 was more than double than necessary according to prevalence of bacterial infections and average duration of treatment. The structure of antibiotics was not in full compliance with the national good practice guidelines, but it was in accordance with data on bacterial antibiotic resistance in outpatient practice. It is necessary to initiate measures to rationalize the use of antibiotics both in terms of quantity and in terms of the structure of the most used antibiotics.

Cefotaxime pharmacokinetics after oral application in the form of 3alpha,7alpha-dihydroxy-12-keto-5beta-cholanate microvesicles in rat.

The aim of ths study was to investigate the pharmacokinetics of cefotaxime sodium (CEF) pharmacokinetics after oral application in the form of sodium 3alpha,7alpha-dihydroxy-12-keto-5beta-cholanate (MKC) microvesicles (MV) in rat. Thirty Male Wister rats were divided into six groups (n=5 per group). Groups were treated orally with: (i) CEF (15 mg/kg) saline solution (15 mg/kg); (ii) CEF (15 mg/kg) saline solution with MKC (2 mg/kg); (iii) CEF saline solution mixed with blank microvesicles; (iv) CEF (15 mg/kg) encapsulated in microvesicles with saline solution; (v) CEF saline solution (15 mg/kg) mixed with blank MKC microvesicules; (vi) CEF (15 mg/kg) encapsulated in MKC microvesicules with saline solution. Data were analyzed using noncompartmental model. CEF oral bioavailability was increased twofold when coadministered with MKC and when encapsulated in microvesicles and ninefold when encapsulated in MKC microvesicles compared to the same CEF dose administered orally as saline solution. The increased bioavailability of CEF resulting from CEF encapsulation in microvesicules with MKC suggests that this formulation can extend the application of CEF from parenteral only to oral application.