PHARMACOKINETIC AND BIOEQUIVALENCE COM-PARISON BETWEEN TELMISARTAN TABLETS 80MG: AN OPEN LABEL, BALANCED, RANDOMIZED-SEQUENCE, SINGLE-DOSE, TWO-PERIOD CROSS-OVER STUDY IN HEALTHY MALE VOLUNTEERS

Abstract

Background: This present bioequivalence study was designed to determine the pharmacokinetic, bioavailability and bioequivalence of telmisartan 80mg tablets in comparison with MICARDIS^TM telmisartan 80mg tablets after single dose administration under fed conditions in healthy adult male subjects. Therefore the design of an open label, balanced, randomized, two-sequence, single dose, two way crossover study with a wash-out period of at least 7 days was used.

Methods: An open-labeled, balanced, single-dose with food, two-treatment, two-period, two-sequence, randomized crossover study was conducted in 20 healthy male volunteers. Each volunteer received a 80mg tablet of the reference or test drug respectively. On the day of dosing, blood samples were collected before dosing and at various time points up to 72 hours after dosing. Analysis of telmisartan concentrations was performed using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. The pharmacokinetic parameters including C_max, AUC_0-t, AUC_0-inf, T_max, t_1/2 and K_el were analyzed using the non-compartmental model. Drug safety and tolerability were assessed.

Results: The pharmacokinetic parameters including C_max, AUC_0-t, AUC_0-inf, T_max, t_1/2 and K_el were analyzed using the non-compartmental model. Drug safety and tolerability were assessed. The primary pharmacokinetic parameters (C_max, AUC_0-t and AUC_0-inf) 90%CI were within the 80 to 125% interval required for bioequivalence as stipulated in the current regulations of the USFDA acceptance criteria. The geometric mean ratios (Test/Reference) between the two products of 80mg tablets under fed condition were 92.34% (92.23%-117.37%) for C_max ratios, 91.84% (94.28%-110.31%) for AUC_0-t ratios and 99.42% (93.65%-106.97%) for AUC_0-inf ratios of Telmisartan. Twenty volunteers had completed both treatment periods. There was no significant difference of the T_max parameter between the two formulations (p >0.05). No serious adverse events related to the study drugs were found.

Conclusion: This single dose study found that the test formulation telmisartan 80mg tablets are bioequivalent to the reference formulation MICARDIS^TM telmisartan 80mg tablets in terms of extent and rate of absorption, under fed condition in healthy adult male volunteers according to the USFDA regulatory guidance.