Absorption and disposition of hydrochlorothiazid

Rat was used as an animal model to study the disposition and absorption kinetics of hydrochlorothiazide. The results obtained from the disposition study show that the unit BSA concept could be used to correlate the kinetic parameters such as clearances (total and unbound) between rats and humans, and based on the interspecies relationship of this drug, the biological T$sb{1/2}$ and Vd$sb{rm area}$ in humans were well predicted based on rat data.;After analysis of the data obtained from the in vitro influx-efflux kinetic study of this drug across RBC membranes and from the in vivo study of renal excretion of this drug across the kidney, it is revealed that the partition of this drug between plasma and RBC is not instantaneous or very fast and the drug in the RBC is not available for renal excretion. The results obtained from the rat study may provide a rationale for the reported different mean peak times of this drug in plasma and RBC after oral dosing in humans.;The results obtained from the oral study also indicate that rat could be a good animal model for studying the gastrointestinal absorption as well as the disposition kinetics. This drug also exhibits dose-independent absorption characteristics in rats based on the plasma and urinary recovery data. Finally, the F was well predicted from a relatively simple intestinal loop absorption study and a similar F could be predicted in humans, since rats and humans may have similarities in gastrointestinal permeability and small intestinal transit time.