Multiple-dose pharmacokinetics of telmisartan and of hydrochlorothiazide following concurrent administration in healthy subjects

This open-label, crossover study had two objectives: to compare the steady- state pharmacokinetics of high-dose telmisartan with and without coadminist ered high-dose hydrochlorothiazide and to compare the steady-state pharmaco kinetics of hydrochlorothiazide with and without coadministered telmisartan . A total of 13 healthy males and females of nonchildbearing potential rece ived the following oral, once-daily medications, each for 7 days: telmisart an 160 mg, hydrochlorothiazide 25 mg, and telmisartan 160 mg plus hydrochlo rothiazide 25 mg. Between medication periods, there was a 14-day washout. B lood was collected at intervals over 48 and 84 hours, respectively at the e nd of the 7-day dosing period for the determination of plasma telmisartan a nd hydrochlorothiazide concentrations by high-performance liquid chromatogr aphy. Predose blood samples were also collected on days 1, 6 and 7 Tolerabi lity of single-agent and combination medication was monitored. For hydrochl orothiazide and telmisartan, given alone or in combination, there were no a ppreciable differences in trough plasma concentrations between days 6, 7 an d 8; thus, at day 7 both agents had achieved steady state. Mean Values of t he primary end points (C-max and AUC(0-24)) and secondary end points (C-min and t(1/2)) for both telmisartan and hyrochlorothiazide were unaffected wh en administered simultaneously. Moreover, concurrent telmisartan had no eff ect on urinary excretion of hydrochlorothiazide. Transient lightheadedness, associated with postural hypotension, was the most common adverse event. T he absence of any significant effects on the pharmacokinetics of either hyd rochlorothiazide or telmisartan shows that no dose adjustment is required i f the two agents are given concurrently for the management of hypertension. (C) 2000 the American College of Clinical Pharmacology.