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Drug combination therapy is the most common pharmacological strategy for hypertension management. No pharmacogenetic biomarkers for guiding hypertension pharmacotherapy are available to date. The study population were 64 volunteers from seven bioequivalence trials investigating formulations with valsartan, olmesartan and/or hydrochlorothiazide. Every volunteer was genotyped for 10 genetic variants in different transporters’ genes. Additionally, valsartan-treated volunteers were genotyped for 29 genetic variants in genes encoding for different metabolizing enzymes. Variability in pharmacokinetic parameters such as maximum concentration (C_max) and time to reach it (t_max), the incidence of adverse drug reactions (ADRs) and blood pressure measurements were analyzed as a function of pharmacogenetic and demographic parameters. Individuals with the <i>ABCB1</i> rs1045642 T/T genotype were associated with a higher valsartan t_max compared to those with T/G and G/G genotypes (<i>p</i> < 0.001, β = 0.821, R² = 0.459) and with a tendency toward a higher postural dizziness incidence (11.8% vs. 0%, <i>p</i> = 0.070). A higher hydrochlorothiazide dose/weight (DW)-corrected area under the curve (AUC_∞/DW) was observed in <i>SLC22A1</i> rs34059508 G/A volunteers compared to G/G volunteers (<i>p</i> = 0.050, β = 1047.35, R² = 0.051), and a tendency toward a higher postural dizziness incidence (50% vs. 1.6%, <i>p</i> = 0.063). Sex impacted valsartan and hydrochlorothiazide pharmacokinetics, showing a lower exposure in women, whereas no significant differences were found for olmesartan pharmacokinetics.