BackgroundThe genetic variation underlying atorvastatin (ATV) pharmacokinetics was evaluated in a Mexican population. Aims of this study were: 1) to reveal the frequency of 87 polymorphisms in 36 genes related to drug metabolism in healthy Mexican volunteers, 2) to evaluate the impact of these polymorphisms on ATV pharmacokinetics, 3) to classify the ATV metabolic phenotypes of healthy volunteers, and 4) to investigate a possible association between genotypes and metabolizer phenotypes.MethodsA pharmacokinetic study of ATV (single 80-mg dose) was conducted in 60 healthy male volunteers. ATV plasma concentrations were measured by high-performance liquid chromatography mass spectrometry. Pharmacokinetic parameters were calculated by the non-compartmental method. The polymorphisms were determined with the PHARMAchip® microarray and the TaqMan® probes genotyping assay.ResultsThree metabolic phenotypes were found in our population: slow, normal, and rapid. Six gene polymorphisms were found to have a significant effect on ATV pharmacokinetics: MTHFR (rs1801133), DRD3 (rs6280), GSTM3 (rs1799735), TNFα (rs1800629), MDR1 (rs1045642), and SLCO1B1 (rs4149056). The combination of MTHFR, DRD3 and MDR1 polymorphisms associated with a slow ATV metabolizer phenotype.ConclusionFurther studies using a genetic preselection method and a larger population are needed to confirm these polymorphisms as predictive biomarkers for ATV slow metabolizers.Trial registrationAustralian New Zealand Clinical Trials Registry: ACTRN12614000851662, date registered: August 8, 2014.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2062-2) contains supplementary material, which is available to authorized users.

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Amfepramone (AFP) is an appetite-suppressant drug used in the treatment of obesity. Nonetheless, studies on interindividual pharmacokinetic variability and its association with genetic variants are limited. We employed a pharmacokinetic and pharmacogenetic approach to determine possible metabolic phenotypes of AFP and identify genetic markers that could affect the pharmacokinetic variability in a Mexican population. A controlled, randomized, crossover, single-blind, two-treatment, two-period, and two sequence clinical study of AFP (a single 75 mg dose) was conducted in 36 healthy Mexican volunteers who fulfilled the study requirements. Amfepramone plasma levels were measured using high-performance liquid chromatography mass spectrometry. Genotyping was performed using real-time PCR with TaqMan probes. Four AFP metabolizer phenotypes were found in our population: slow, normal, intermediate, and fast. Additionally, two gene polymorphisms, ABCB1-rs1045642 and CYP3A4-rs2242480, had a significant effect on AFP pharmacokinetics (P < 0.05) and were the predictor factors in a log-linear regression model. The ABCB1 and CYP3A4 gene polymorphisms were associated with a fast metabolizer phenotype. These results suggest that metabolism of AFP in the Mexican population is variable. In addition, the genetic variants ABCB1-rs1045642 and CYP3A4-rs2242480 may partially explain the AFP pharmacokinetic variability.

Introduction and Objectives: Allergic rhinitis is a condition with high global prevalence most effectively treated with antihistamines and antileukotrienes. This study aimed to evaluate the bioequivalence of fexofenadine and montelukast in a fixed-dose combination tablet versus the components administered simultaneously.Materials and Methods: An open, randomized, 2×2 crossover study was performed in 78 healthy volunteers. Fexofenadine–montelukast tablets containing 120 mg and 10 mg, respectively, were used as the test treatment, and 120 mg fexofenadine tablets and 10 mg montelukast tablets were used as the reference treatment. Concentrations of fexofenadine and montelukast in plasma were determined by protein precipitation and analysis by liquid chromatography/mass spectrometry or liquid chromatography tandem mass spectrometry.Results: The 90% confidence intervals (CIs) obtained for fexofenadine were 87.612–102.144 for area under the curve of the plasma concentration after administration to the last concentration (AUC0-t), 88.471–102.282 for the AUC of the plasma concentration extrapolated to infinity (AUC0–∞), and 91.413–108.544 for the maximum plasma concentration (Cmax). For montelukast, they were 96.418–108.416 for AUC0-t, 93.273–106.642 for AUC0-∞ and 94.749–110.178 for Cmax. The ratio and CIs of the values subjected to logarithmic transformation for each parameter were within the range of acceptability of 80%–125%, demonstrating the bioequivalence of the combined fixed-dose tablet to the components administered separately at the same doses. No adverse events were recorded during the study.Conclusions: This study has shown the bioequivalence of the combined fixed-dose tablet, which may be considered a new alternative for the treatment of allergic rhinitis.

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