Abstract
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.
Footnotes
- Received March 5, 1974.
- Copyright © 1974 by The American Society for Pharmacology and Experimental Therapeutics
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