COMPARATIVE IN-VITRO AND IN-VIVO BIOAVAILABILITY OF A PROPRIETARY ANDA GENERIC HYDROCHLOROTHIAZIDE PRODUCT

A dose of 100 mg of hydrochlorothiazide as contained in a proprietary (Moduretic(R)) and a generic (Ami-hydrotride(R)) preparation was admin istered to 12 fasting healthy subjects on two separate occasions, sepa rated by a 2 week washout period, in an open, randomised, cross-over s tudy. Blood samples were withdrawn periodically, and plasma hydrochlor othiazide concentrations were measured by HPLC. The area (AUC(0-24h)) under the plasma concentration time curve for the proprietary (Moduret ic(R)) and generic (Ami-hydrotride(R)) preparations (6911 ng/h/ml vers us 8659 ng/h/ml) and maximum plasma concentration Cp(max) (808 ng/ml v ersus 743 ng/ml) were similar but the time to reach maximum plasma con centration, t(max), for Moduretic(R) was significantly (p < 0.05) shor ter than that for Ami-hydrotride(R) (2.1 h versus 3.9 h). In vitro par ameter of percentage dissolved at 1, 2 and 5 min of Ami-hydrotride(R) was significantly (p < 0.05) longer than Moduretic(R).