Clinical Pharmacokinetics of Hydralazine

SummaryHydralazine is widely used as a peripheral vasodilator antihypertensive drug. During recent years, knowledge has accumulated on the pharmacokinetics of hydralazine in man. It is subjected to polymorphic N-acetylation, with phenotypically slow acetylators having higher steady state plasma concentrations and higher bioavailability of the drug in single dose studies, compared with subjects who are fast acetylators. However, the terminal elimination half-life of hydralazine is only slightly longer among slow acetylators, thus it does not seem very likely that polymorphic N-acetylation can represent the major metabolic pathway of the drug in man. Hydrallazine is subject to significant first-pass metabolism and there are indications that the N-acetylation process involved may be capacity-limited.About 10% of a single oral dose can be recovered from the urine as the parent drug, but in spite of the apparent independence of renal function for its elimination thus suggested, hydrallazine is eliminated at a considerably slower rate in uraemic patients; possibly as a consequence of impaired hepatic metabolism or underestimation of the amount excreted unchanged in subjects with normal renal function. In spite of very high steady state plasma concentrations and prolonged clearance of hydrallazine in renal failure, no harmful effects have been reported. At least 2 active metabolites have been identified, but their clinical importance and kinetic properties have not been elucidated.The duration of the hypotensive effect of hydrallazine exceeds that predicted from the rate of elimination of the parent compound from plasma. Since there is no clear-cut correlation between the plasma concentration of the drug and its effect upon blood pressure, there is at present no reason to routinely measure plasma levels of hydrallazine in treated hypertensive patients.