ABSTRACT
The kinetics of absorption of hydrochlorothiazide was studied in four adult male volunteers. Plasma levels were monitored for 48 h after a 100-mg dose. Food, electrolyte, and water intake were regulated as far as possible. The plasma level data were fitted to a two-compartment open model with either first-order or zero-order absorption, using the pharmacokinetic computer program AUTOAN. A better fit of the data, both graphically and statistically, was obtained with zero-order absorption kinetics. Additional confirmation of absorption kinetics was obtained by treating the plasma level results by the Loo-Riegelman method. Cartesian graphs of the amount absorbed verus time afforded linear plots, which indicate a zero-order process.
Subject(s)
Hydrochlorothiazide/metabolism , Administration, Oral , Adult , Humans , Hydrochlorothiazide/blood , Intestinal Absorption , Kinetics , Male , Middle Aged , Models, BiologicalABSTRACT
Derivatization of hydralazine in plasma under acidic conditions yields values for the concentrations of "apparent" hydralazine that are dependent on the pH in the derivatization step. The results have been explained by postulating the existence of acid-hydrolyzable conjugates of unknown structure. These metabolites appear to be present in rat and human plasma after oral dosing. Procedures have been developed for the selective analysis of hydralazine or its acid-labile conjugates, and applied to measurements of plasma concentrations in rat and man.
