Effect of the combination of lisinopril and hydrochlorothiazide on the bioequivalence of tablet formulations.

Rossen Koytchev, Yildiz Ozalp, Aydin Erenmemisoglu, Mike John van der Meer, Recep Serdar Alpan

Cooperative Clinical Drug Research and Development, Neuenhagen, Germany. mail@ccdrdag.com

Arzneimittel-Forschung 2004 Sep

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The aim of the present studies, performed in two different groups of volunteers, was to compare the bioavailability of 20 mg lisinopril tablets (Sinopryl as test and an orignator product as reference formulation; study 1) and lisinopril/hydrochlorothiazide (20 mg/12.5 mg) (CAS 83915-83-7/CAS 58-93-5) combined formulations (Sinoretik as test and an originator product as reference formulation; study 2). Each study was conducted according to an open, randomized, single-dose, two-period cross-over design in healthy volunteers with a wash-out period from 7 to 14 days. Blood samples were taken up to 72 h in both studies, the plasma was separated. Concentrations of lisinopril and hydrochlorothiazide were determined by HPLC-MS-MS method. In the first study, the 90% confidence interval for intra-individual ratios of AUC0-t and Cmax of lisinopril were between 0.85 and 1.12 (AUC0-t) and between 0.87 and 1.17 (Cmax), and thus within the acceptance ranges. In the second study, i.e. after administration of combined lisinopril/hydrochlorothiazide formulations, the 90% confidence interval for intra-individual ratios of AUC0-inf and Cmax of lisinopril were between 0.83 and 1.22 (AUC0-inf) and between 0.80 and 1.25 (Cmax). The 90% confidence interval for intra-individual ratios of AUC0-inf and Cmax of hydrochlorothiazide were between 0.92 and 1.04 (AUC0-inf) and between 0.88 and 1.08 (Cmax). All the above values were within the acceptance ranges for bioequivalence studies. In the light of the present studies it can be concluded that Hsinopril as well as lisinopril/hydrochlorothiazide test formulations are bioequivalent to the respective reference formulations.

Citation

Rossen Koytchev, Yildiz Ozalp, Aydin Erenmemisoglu, Mike John van der Meer, Recep Serdar Alpan. Effect of the combination of lisinopril and hydrochlorothiazide on the bioequivalence of tablet formulations. Arzneimittel-Forschung. 2004 Sep;54(9A):605-10