Hydralazine elimination in man

The metabolism of hydralazine has been studied in a series of experiments. The hydralazine plasma half‐life values in volunteers ranged from 2.2 to 7.8 hours in rapid acetylators and from 2.0 to 5.8 hours in slow acetylators. Plasma concentrations following intravenous administration were similar in slow and rapid acetylators, indicating similar volumes of distribution of hydralazine. Plasma concentrations of hydralaZine following oral administration were lower in rapid acetylators than in slow acetylators, indicating a difference in gut wall and liver “first pass” metabolism since it has been shown by Lesser and associates 7 that the molecule is well absorbed. Patients with impaired renal function had higher plasma concentrations of hydralaZine at various times after an oral dose than those with normal renal function. The metabolism of hydralaZine includes nonenzymatic degradation to phthalazine at a rate of 0.07 p.g per milliliter per hour in plasma at 37° C. Phthalazine may be subsequently enzymatically metabolized as well as excreted. There is metabolism by the intestinal wall or liver during absorption or “first pass” that is related to genetic acetylator phenotype. There is further biotransformation as well as excretion of the acetylated metabolite. This “first pass” acetylation by the intestinal wall and liver represents a true detoxication mechanism for inactivating orally administered hydralazine. There is also an elimination process that is unrelated to acetylator phenotype.