Determination of triamterene and its main metabolite hydroxytriamterene sulfate in human urine by capillary electrophoresis using ultraviolet absorbance and laser-induced fluorescence detection.

Two capillary electrophoresis methods have been developed for the direct determination of triamterene and its main metabolite hydroxytriamterene sulfate in human urine. Analytes were detected using conventional UV detection as well as laser-induced fluorescence (LIF) detection with an HeCd-laser operating at a wavelength of 325 nm. The results of both detection techniques were compared. Indeed, the limit of quantification was eightfold lower using LIF detection (50 ng/ml) in comparison to UV detection (400 ng/ml). As no interference due to endogenous urine compounds was observed, direct urine analysis was feasible. Analysis was very simple and fast-one run could be performed within less than 10 min (CE-UV method) and 2.5 min (CE-LIF method), respectively. Both assays were fully validated and applied to urine samples from a human volunteer. The results of the application of the CE-LIF method to human urine samples are presented in this publication.

Pharmacodynamic studies on the angiotensin II type 1 antagonists irbesartan and candesartan based on angiotensin II dose response in humans.

The in vivo effects of two unsurmountable angiotensin II type 1 (AT1) antagonists, irbesartan (150 mg) and candesartan (8 mg), were studied in a double-blind, randomized, crossover study in 18 healthy men. The drugs' direct vascular effects were assessed as the rightward shift (dose ratio - 1) of angiotensin dose-effect curves on diastolic blood pressure (DBP). Renal and adrenal effects were assessed by plasma renin activity (PRA), aldosterone concentrations, and antagonistic concentration equivalents (n x Ki) in a radioligand rat lung receptor assay. Both drugs exerted similar substantial (> 30-fold) and long-lasting (> 2-fold 47 h after dosing) rightward shifts of the angiotensin II dose effect declining with half-lives of 15 h irbesartan and 12 h candesartan, respectively. Dose ratio - 1 versus n x Ki showed a linear relationship in Schild regression plots; both drugs increased PRA, decreased DBP, and suppressed aldosterone. The slopes of linear relationship between angiotensin antagonism (dose ratio - 1) and PRA increase were almost threefold steeper (p = 0.005) following irbesartan as compared with candesartan. The findings suggest that for the same degree of angiotensin II antagonism, irbesartan produces a greater increase in PRA than candesartan. These pharmacodynamic differences warrant further investigation and clarification.