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

• Published in: Razrabotka i registraciâ lekarstvennyh sredstv (Online) Vol. 9; no. 4; pp. 155 - 163
• Main Authors: Kubesh, V., Khokhlov, A. L., Shitova, A. M., Dzhurko, Yu. A., Kazey, V. I., Khokhlov, A. A., Miroshnikov, A. E., Lebedeva, O. V., Klaus, I. K., Zyatenkov, A. V.
• Format: Journal Article
• Language: English; Russian
• Published: LLC Center of Pharmaceutical Analytics (LLC «CPHA») 26.11.2020
• Subjects: амлодипин; биоэквивалентность; телмисартан; фармакокинетика
• ISSN: 2305-2066; 2658-5049
• DOI: 10.33380/2305-2066-2020-9-4-155-163

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 Cmax and AUC0-72 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 AUC0-72, and 76.73–130.32 % for Cmax. Conclusion . Thus, according to the criteria used in the study, the formulations are proved to be bioequivalent.