Pharmacokinetic and Bioequivalence Study of Telzap AM^® (Telmisartan/amlodipine Fixed-dose Combination) and Coadministered Mikardis^® (Telmisartan) and Norvask^® (Amlodipine) in Healthy Subjects

Introduction. A fixed dose combination of telmisartan and amlodipine is widely used in clinical practice during hypertension treatment. Combination of telmisartan and amlodipine demonstrates potentiating synergistic effect on blood pressure decrease. A bioequivalence study of Telzap® AM with coadministered Mikardis® and Norvask® was conducted with 60 volunteers.

Aim. The purpose of the bioequivalence trial was a comparative study of the pharmacokinetics and evidence of the bioequivalence of the fixed dose combination drug product Telzap® AM (telmisartan + amlodipine, tablets, 80 + 10 mg, Zentiva ks company, Czech Republic) and coadministrated monocomponent drug products Mikardis® (telmisartan, tablets 80 mg, Beringer Ingelheim International GmbH, Germany) and Norvask® [amlodipine, tablets 10 mg, Pfizer HCP Corporation (USA), Russia] in healthy volunteers after a single administration under fasting.

Materials and methods. To prove bioequivalence, an open label, comparative, randomized, crossover four-period replicate clinical trial was conducted. The concentrations of amlodipine and telmisartan in plasma samples were determined by a validated HPLC-MS/MS method. A pharmacokinetic and statistical analysis was performed and confidence intervals for the pharmacokinetic parameters C_max and AUC_0-72 were calculated.

Results and discussion. It can be concluded that the studied formulations are bioequivalent in terms of pharmacokinetic parameters of amlodipine and telmisartan. All 90 % confidence intervals for the estimated pharmacokinetic parameters of amlodipine were in the range of 80–125 %, 90 % confidence intervals for telmisartan were within the bioequivalence range of 80–125 % for AUC_0-72, and 76.73–130.32 % for C_max.

Conclusion. Thus, according to the criteria used in the study, the formulations are proved to be bioequivalent.

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