Distribution of elimination of hydroflumethiazide in man

The pharmacokinetics of hydroflumethiazide (HFT) were investigated after intravenous and oral administration to healthy subjects. After intravenous infusion, HFT behaved according to a three-compartment model. Two distribution phases were observed, with mean half-lives of 0.26 and 0.85 h, reflecting distribution to red blood cells and tissues. Mean biological half-life (t 1/2 beta) after infusion was 5.2 h. Renal blood and plasma clearance of HFT, as well as the ratio renal blood clearance/renal plasma clearance of HFT, were lower after infusion than during the infusion, due to the distribution characteristics of HFT. After a single oral dose of 2 micronmol/kg, t 1/2 beta was significantly shorter in all subjects than after a single oral dose of 6 micronmol/kg, with mean t 1/2 beta of 8.7 and 17.9 h, respectively. Due to lack of a sufficiently sensitive method for determination of HFT in plasma, it could not be established whether the observed dose-dependent difference in biological half-life of HFT was caused by variation in renal clearance and/or the volume of distribution.