Kinetics of hydrochlorothiazide absorption in humans.

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.

Plasma levels of real and "apparent" hydralazine in man and rat.

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.

Fully automated analysis of phenylbutazone in plasma and urine.

A rapid, automated method for the determination of phenylbutazone in plasma and urine was developed. The method offers distinct advantages over earlier procedures and is particularly suitable for large-scale bioavailability studies.

The objective and timing of drug disposition studies, appendix I. Species differences in the tissue distribution of metazimid, an imidazolone derivative.

A marked species difference has been observed in the tissue distribution of metazimid in the rat vs the dog after repeated doses. Differences in toxicity between these species are consistent with tissue levels but not plasma levels. No species differences in patterns of drug metabolism could be found in association with the marked difference in tissue cumulation.

The objective and timing of drug disposition studies, appendix IV. Phenylbutazone formulations: in vitro dissolution and in vivo performance.

Human plasma level studies were conducted on various phenylbutazone formulations. The resultant data indicated that the nature of the formulation had a marked influence on the rate of phenylbutazone absorption. An in vitro dissolution rate apparatus was employed in an attempt to predict potential absorption of phenylbutazone from a given formulation. Based upon the in vitro-in vivo correlation, a new phenylbutazone tablet product was developed which produced a complete and more rapid absorption of the drug.