Hydralazine kinetics in hypertensive patients after intravenous administration

Previous studies on intravenous hydralazine kinetics have been performed using nonselective analytical techniques that measure not only hydralazine but also certain hydralazine metabolites such as hydralazine pyruvic acid hydrazone (HPH). We studied the time course of hydralazine and HPH in eight hypertensive patients after 0.3 mg/kg intravenously with selective high-pressure liquid chromatographic assays. “Apparent” hydralazine concentrations were also determined using a nonselective gas-liquid chromatographic procedure. Total plasma clearance, CLT[72.9 ±4.9 (SEM) ml · min−1 · kg−1], apparent volume of distribution, Vdarea (5.83 ± 0.30 l · kg−1), steady-state volume of distribution, Vdss(1.83 ± 0.17 · kg−1), and terminal half-life, t½ (53.7 min, harmonic mean) were independent of acetylator phenotype. The high CLT is compatible with rapid intravascular conversion of hydralazine to HPH and a high hepatic extraction ratio. Peak HPH concentrations occurred 10 to 60 min after dose; mean HPH t½ was 239 min. “Apparent” hydralazine concentrations were usually highest in the 2-min plasma sample and declined with a mean t½ of 296 min. Reports based on nonselective assay methods have underestimated CLT, Vdss, and Vdarea and have overestimated the t½ of hydralazine. Clinical Pharmacology and Therapeutics (1980) 28, 736–742; doi:10.1038/clpt.1980.229