Kinetics of hydralazine and its main metabolites in slow and fast acetylators.

摘要: Kinetics of hydralazine (HP) and its metabolites, pyruvic acid hydrazone (HPPAH) 3-methyl-s-triazolo[3,4-a]phthalazine (MTP), was examined in five slow fast acetylators after single oral intravenous doses HP on separate occasions at least 1 wk apart. Blood samples were collected over a 10-hr period levels the drug metabolites determined by sensitive high-performance liquid chromatographic -fluorescence assay. After administration plasma concentrations fitted to two-compartment model following mean kinetic parameters obtained for acetylators: terminal half Ufes (t1/2s), 0.677 0.664 hr; total clearances, 7.77 8.86 l/hr/kg; distribution pseudoequilibrium t½s, 4.80 5.40 min; volumes compartment, 2.53 3.01 l/kg; steady-state distribution, 5.71 6.37 apparent volume (calculated from clearance divided β, where β is compound rate constant expressing loss body achieved), 7.25 8.16 l/kg. None different (i.e., statistically) two groups. Of those measured, major metabolite HPPAH, which together with constituted most “apparent HP” measured published nonspecific assays. The areas under curve (AUCs) MTP 0.501 1.014 μm/l/hr (p 0.6) bioavailability, 35.4% 16.2% < 0.001). With this route administration, HPPAH acetylators. AUCs (corrected dose differences) 1.50 3.98 0.001) acetylators. Clinical Pharmacology Therapeutics (1980) 28, 769–778; doi:10.1038/clpt.1980.234