No abstract

14C‐hydrochlorothiazide (hct) was administered orally (n = 4) and iv (n = 2) to healthy subjects. The gastrointestinal absorption ranged between 60% and 80%, most of it took place in the duodenum and the upper jejunum. The radioactivity was eliminated mainly in the urine, while no significant biliary excretion was observed. Chromatographic analysis of the urinary radioactivity demonstrated that >95% of the absorbed or injected 14C‐hct was excreted unchanged. The radioactivity in plasma during the first 10 hr after oral administration declined with a fast phase but the levels of label thereafter suggested a slow phase. The existence of such a phase was verified in 1 subject given 75 mg hct orally. His plasma levels of hct (determined with gas‐liquid chromatography) declined according to a 2‐compartment model, the half‐lives of the α− and β‐phases being 1.7 and 13.1 hr, respectively. Hct accumulated in the blood cells and the ratio between the radioactivity in cells and that in plasma averaged 3.5. The fate of a single dose of 14C‐hct in 2 hypertensive patients treated with the drug chronically was similar to that in the healthy subjects. A third patient, who had slightly elevated serum creatinine, eliminated hct more slowly than the others. Like the healthy subjects, the patients eliminated hct

Nine previously untreated hypertensive patients (WHO Stage I and II) were given hydrochlorothiazide (hct) 12.5, 25, 50 and 75 mg for two weeks after an initial four week period of placebo treatment. Blood pressure recordings were made casually and after 30 min rest in lying, sitting and standing positions. Plasma concentrations of the drug were measured by GLC. A significant decrease in BP was seen during treatment with hct 12.5 mg except in the casual standing position. Doubling of the dose twice produced very little further decrease in BP. The mean steady state concentration was 111 ng.ml-1 during treatment with hct 75 mg. A linear relationship was found between the plasma concentration of hct at 0 and 5 h and the various dose level of hct. No relation was found between plasma concentration and reduction in blood pressure.

Hydrochlorothiazide 775mg was administered orally to 5 patients who had undergone intestinal shunt operations for obesity 1.5 to 6 years previously. Postoperative weight loss averaged 53.4kg. The concentrations of hydrochlorothiazide in plasma and urine were determined with gas/liquid chromatography. The mean area under the plasma concentration time curve during 9h in 4 of the patients was 889ng/ml.h. Mean total urinary recovery of hydrochlorothiazide amounted to 23.0mg in the 5 patients, which corresponds to approximately half that seen in healthy volunteers. The gastrointestinal hydrochlorothiazide appears to be substantially reduced after intestinal shunt surgery.

1Hydrochlorothiazide (HCT, 50-75 mg) was administered orally to seven patients with cardiac failure. 2 Plasma levels and urinary concentration of HCT were determined by GLC. 3 The gastrointestinal uptake of the diuretic in three patients was reduced to approximately half that seen in healthy controls. 4 Plasma hailfife of HCT was correlated with endogenous creatinine clearance. 5Pharmacokinetics of HCT are considerably changed in cardiac failure.