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The relationships between dosage, plasma concentration, and hypotensive action of hydralazine were examined in 20 patients with essential hypertension. Plasma hydralazine was assayed with a method which allowed measurement of concentrations as low as 0.05 µg per milliliter. The relation between dose and plasma level of hydralazine varied fourfold among patients but remained constant in individual subjects over several weeks. Acetylation phenotype, as determined by sulfamethazine acetylation rate, was an important determinant of the plasma level of hydralazine. The ratio of plasma concentration to daily dose of hydralazine averaged 1.7 times higher in slow acetylators than in fast acetylators. Plasma concentrations of hydralazine were also increased in patients with impaired renal function. The dose of hydralazine required for satisfactory blood pressure reduction was 58 per cent higher in fast acetylators than in slow acetylators. ln both phenotypes, the plasma concentration of hydralazine correlated well with the magnitude of its hypotensive effect. Determinations of plasma levels during the therapeutic use of hydralazine may be useful guides to effective and safe dosage.
Zacest et al. (Mon,) studied this question.