Pharmacokinetics of a telmisartan, amlodipine and hydrochlorothiazide fixed-dose combination: A replicate crossover study in healthy Korean male subjects

Purpose: To compare the tolerability and pharmacokinetic profiles of telmisartan, amlodipine, and hydrochlorothiazide (HCTZ) in a fixed-dose combination (FDC, test product) with a co-administered telmisartan/amlodipine FDC and HCTZ in a single-entity tablet (reference product) Methods: This was a single-dose, randomized, open-label, replicate crossover study conducted in healthy male Korean volunteers aged 19-50 years. Fasting randomized subjects received a newly developed test product (telmisartan/amlodipine/HCTZ, 80/10/25 mg) or two tablets of Twynsta (R) (40/5 mg) and one tablet of HCTZ (25 mg) as reference products. After a washout period, each group replicated the exposure of the other group. Results: The AUClast (h.ng/mL) geometric mean was 3,194.87 and 3,273.77 for the telmisartan test and reference products, respectively; 329.92 and 315.13 for the amlodipine test and reference products; 1,203.98 and 1,150.86 for the HCTZ test and reference products, respectively. The geometric mean of C-max (ng/mL) was 543.04 and 497.81 for the telmisartan test and reference products, respectively; 7.74 and 7.34 for the amlodipine test and reference products; 218.71 and 184.39 for the HCTZ test and reference products, respectively. For telmisartan, the 90 % CI of GMRs of AUC(last) (h.ng/mL) and C-max (ng/mL) were 0.9414-1.0496 and 1.0246-1.2792, respectively; the coefficient of variation (CV) of telmisartan Cmax was 41.96 %. Conclusion: A formulated FDC tablet containing a telmisartan/amlodipine/HCTZ combination (80/10/25 mg) was bioequivalent to a co-administrated commercially available telmisartan/amlodipine combination and HCTZ tablets at equivalent concentrations.