Hydralazine kinetics after single and repeated oral doses

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Abstract
In reports on hydralazine kinetics, plasma hydralazine levels have been measured with nonspecific assay techniques. The techniques used also include acid-labile hydralazine metabolites and therefore markedly overestimate hydralazine levels. Specific, sensitive assay methods for the measurement of hydralazine and its major plasma metabolite, hydralazine pyruvic acid hydrazone (HPH) were developed. By these methods, hydralazine and HPH kinetics were determined after single and repeated oral doses of hydralazine in 8 hypertensive patients. Hydralazine bioavailability in the fast acetylator group (9.5% single dose, 6.6% repeated doses) and in the slow acetylator group (31.3% single dose, 39.3% repeated doses) was phenotype dependent. Peak plasma levels were lower than those reported with nonspecific assays: 0.32 .mu.M for the single dose and 0.14 .mu.M for repeated doses in the fast acetylator group and 1.03 .mu.M for the single dose and 0.96 .mu.M repeated doses in the slow acetylator group. There was no alteration in kinetics and no cumulation in plasma on repeated administration. HPH plasma levels were proportional to those of hydralazine in both acetylator groups and were 2.5 to 4 times as high as those of hydralazine. Elimination half-lifes were phenotype independent, ranging from 4 to 6 h. HPH cumulated in the rapid but not in the slow acetylator group after repeated hydralazine doses.