Abstract
BackgroundThe pharmacokinetics (PKs) and pharmacodynamics (PDs) of telmisartan varies among the individuals, and the main causes remain unknown. The aim of this study was to evaluate the impact of ORM1, as well as ABCC2, ABCB1, ABCG2 and SLCO1B3 polymorphisms, on the disposition of the drug and BP change after taking 40 mg telmisartan in 48 healthy Chinese males.MethodA total of 48 healthy males were included in this trial. Every volunteer ingested a single dose of 40 mg telmisartan, and the plasma drug concentration and blood pressure (BP) were measured up to 48 h.ResultIn this study, the area under the plasma concentration-time curve (AUC) in the heterozygotes of ORM1 113AG was higher than that in the wild-type homozygotes, AUC(0–48) (113AA vs. 113AG, 1,549.18±859.84 ng·h/ml vs. 2,313.54±1,257.71 ng·h/ml, P = 0.033), AUC(0–∞) (113AA vs. 113AG, 1,753.13±1,060.60 ng·h/ml vs. 2,686.90±1,401.87 ng·h/ml, P = 0.016), and the change(%) of the diastolic blood pressure (DBP) from the baseline BP value also showed a significant difference between the ORM1 113AG and 113AA genotypes at 5 h after taking telmisartan (P = 0.026). This study also showed that the allele of ABCC2 C3972T would affected the disposition of telmsiartan and the DBP change significantly after taking the drug. However, the common SNPs of ABCG2 C421, ABCB1 C3435T, and SLCO1B3 T334G showed no impacts on the PKs of telmisartan or BP change(%) in our trial.ConclusionThe ORM1 A113G polymorphism was associated with the PKs variability after taking telmsiartan, as well as ABCC2 C3972T. The heterozygotes of ORM1 113AG showed a larger AUC and a notable BP change(%) from the baseline compared with the wild-type.Trial RegistrationChinese Clinical Trial Registry ChiCTR-TNC-10000898
Highlights
There are about 1 billion hypertension patients worldwide and the number is still sharply increasing
The ORM1 A113G polymorphism was associated with the PKs variability after taking telmsiartan, as well as ABCC2 C3972T
The heterozygotes of ORM1 113AG showed a larger area under the plasma concentration-time curve (AUC) and a notable blood pressure (BP) change(%) from the baseline compared with the wild-type
Summary
There are about 1 billion hypertension patients worldwide and the number is still sharply increasing. In the healthy volunteers and hypertensive patients, a remarkable inter-individual variability had been reported with the peak concentration in plasma (Cmax) and the area under the plasma concentration-time curve (AUC) of telmisartan [3,4,5,6]. There were a few studies focused on the pharmacogenetics of telmisartan, the discoveries contributed little to the variability of pharmacokinetics (PKs). The variability of the pharmacokinetics (PKs) of telmisartan may occur in the absorption, distribution, or excretion processes. The pharmacokinetics (PKs) and pharmacodynamics (PDs) of telmisartan varies among the individuals, and the main causes remain unknown. The aim of this study was to evaluate the impact of ORM1, as well as ABCC2, ABCB1, ABCG2 and SLCO1B3 polymorphisms, on the disposition of the drug and BP change after taking 40 mg telmisartan in 48 healthy Chinese males
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