Pharmacokinetics of hydroflumethiazide during repeated administration in congestive heart failure

The renal elimination and accumulation of hydroflumethiazide (HFT) during repeated oral administration was investigated in patients with congestive heart failure (CHF). When four doses of HFT wee given with 24 hr intervals, the mean 24 hr urinary excretion of HFT was 55-65% of the dose after 75 mg and 53-57% after 150 mg. 24 hr excretion of HFT was not significantly higher after the fourth dose as compared with the first. The renal plasma clearance of HFT was significantly correlated with creatinine clearance (P less than 0.01). The biological half-life (t1/2 beta) of HFT ranged from 6.5-27.9 hrs. Mean t1/2 beta was shorter (P less than 0.05) after 75 mg (9.2 hrs) than after 150 mg doses (14.1 hrs). The disposition rate constant of HFT was not significantly correlated with creatinine clearance or with renal plasma clearance of HFT, indicating that the volume of distribution was reduced at reduced renal function.