TY - JOUR T1 - METABOLISM AND DISPOSITION OF HYDRALAZINE-<sup>14</sup>C IN MAN AND DOG JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 351 LP - 360 VL - 2 IS - 4 AU - J. M. LESSER AU - Z. H. ISRAILI AU - D. C. DAVIS AU - P. G. DAYTON Y1 - 1974/07/01 UR - http://dmd.aspetjournals.org/content/2/4/351.abstract N2 - Hydralazine-1-14C·HCl (HP-14C·HCl) was administered orally (in solution) to human subjects. The drug was quickly and almost completely absorbed. With 50-100-mg doses, peak plasma levels were 1-2 µg of HP-14C·HCl equivalent per ml; only a small fraction of 14C consisted of HP. The concentration of 14C in red cells was lower than in plasma. The drug was rapidly eliminated, mainly via urine (in 3 and 6 hr. 33-43 and 54-58% of the dose was excreted). The drug is unstable in plasma at 37°C; decomposition can be prevented with Na2EDTA. This finding facilitated measurements of the binding of HP (at pH 7.4 and 37°C) and certain of its metabolites to human plasma and albumin. The binding of HP-14C was fairly high (87% to human plasma at clinically significant concentrations). In dogs given HP-14C·HCl iv, the pattern of elimination was found to be similar to that in man, but binding to dog plasma was lower (71%) than to human plasma. The probability of the formation, of unknown metabolites of HP was indicated by experiments in which one of its metabolites, methyltriazolophthalazine-14C was administered to rats; this compound was found to be further metabolized to several products. Copyright © 1974 by The American Society for Pharmacology and Experimental Therapeutics ER -