Endralazine - a new hydralazine-like antihypertensive with high systemic bioavailability

Endralazine (E), a new hydralazine-like antihypertensive was given intravenously (0.05 mg/kg) to 10 normal volunteers (5 slow and 5 fast acetylators). Plasma levels were fitted to a 3 compartment model and pharmacokinetic parameters (area under curve [AUC infinity 0], clearance, volume of distribution, half-lives) obtained in the usual way. Bioavailabilities of 5 and 10 mg oral doses of E were determined from the AUC infinity 0 generated in a previous study of oral E given to the same subjects. E had high system bioavailability (73.5-99.1%) suggesting that it was almost completely absorbed without undergoing appreciable first-pass metabolism. Furthermore, dose size and acetylator phenotype did not significantly affect the bioavailability of E. This behavior contrasts with that of hydralazine where systemic bioavailability was less than 40%, and 2 to 3 times higher in slow acetylators than in fast acetylators. It is concluded that the bioavailability of E is high and not influenced by acetylator phenotype; these properties suggest some clinical advantages for the drug.