Pharmacokinetics and safety of olmesartan medoxomil in combination with glibenclamide in healthy volunteers.

OBJECTIVE

To investigate the pharmacokinetic interactions, safety, and tolerability of the combination of olmesartan medoxomil with glibenclamide.

METHODS

In an open, three-way crossover, phase I trial, 18 healthy adults entered three randomly ordered, seven-day treatment periods. The three treatments comprised once daily administration of (1) olmesartan 20 mg, (2) olmesartan 20 mg plus glibenclamide 3.5 mg, or (3) glibenclamide 3.5 mg.

RESULTS

The combination of olmesartan with glibenclamide did not influence the bioequivalence of the area under the plasma-concentration time curve at steady state during one dosing interval 0 to tau = 24 hours (AUCss,tau) or the maximum steady-state concentration (Css,max) of both substances. Mean AUCss,tau values for olmesartan were 2594.8 ng h/ml for olmesartan alone and 2443.7 ng h/ml in combination with glibenclamide; the corresponding Css,max values were 479.3 ng/ml and 462.7 ng/ml, respectively. For glibenclamide, the mean AUCss,tau values were 525.7 ng x h/ml for monotherapy and 518.7 ng x h/ml for its combination with olmesartan. The median time to reach Css,max (tmax) for glibenclamide was shifted from 2.0 h to 1.0 h when combined with olmesartan, whereas the median tmax values for olmesartan remained unchanged at 1.5 h. During combined treatment with olmesartan plus glibenclamide, no adverse event occurred, and the medications were well tolerated.

CONCLUSION

With the exception of a slight shift of tmax values for glibenclamide, the concomitant administration of olmesartan medoxomil with glibenclamide had no significant effects on the steady-state pharmacokinetics of either agent. This provides the pharmacokinetic rationale for clinical studies to test the combination therapy of patients with hypertension and type-2 diabetes mellitus with both compounds.