Summary
Five and 10 mg single oral doses of a new vasodilator antihypertensive, endralazine (E) were given on separate occasions to 17 normal male volunteers (8 slow, 7 heterozygous fast and 2 homozygous fast acetylators). The homozygous fast acetylators were excluded from statistical comparisons. Only small differences were observed in the pharmacokinetics of E between the phenotypes and there was no evidence of non-linearity at the 2 dose levels studied. Terminal half-lives ranged from 2.59 to 7.14 h with a mean of 4.30±1.08 h for the 5 mg dose and 4.25±1.09 h for the 10 mg dose. There was no significant difference in half-lives between slow and heterozygous fast acetylators. The mean area under the plasma level-time curve (AUC ∞0 ) was 18.2% lower (p<0.05) in the heterozygous fast acetylators than in the slow acetylators following the 5 mg dose and 11.0% lower (p>0.05) following the 10 mg dose. Extremely rapid absorption of the drug precluded accurate estimation of absorption rates. The AUC ∞0 of the acetylation metabolite (methyltriazoloendralazine) was small compared to that of E although higher in the heterozygous fast acetylators than in the slow acetylators (p<0.01).
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References
Oates HF (1980) Profile of a new vasodilator antihypertensive agent endralazine (BQ 22708). Med J Aust 1: 393
Salzmann R, Bürki H, Chu D, Clark B, Marbach P, Markstein R, Reinert H, Seigl H, Waite R (1979) Pharmakologische Wirkungen des Antihypertensivums 6-Benzoyl-3-hydrazino-5, 6, 7, 8-tetrahydropyrido [4,3-c]pyridazin (BQ 22-708, Endralazin). Arzneim-Forsch 29: 1843–1853
Rubi FC (1978) Role of physical factors in the acute changes in renal function elicited by antihypertensive drugs. Eur J Clin Pharmacol 13: 185–193
Unterhalt B (1978) 6-Benzoyl-3-hydrazino-5, 6, 7, 8-tetrahydropyrido [4,3-c]pyridazine, BQ 22-708. Drugs Future 13: 375–376
Reece PA (1981) Hydralazine and related compounds: chemistry, metabolism and mode of action. Med Res Rev 1: 73–96
Elliot HL, McLean K, Sumner DJ, Donnelly RJ, Reid JL (1982) Clinical evaluation of endralazine (BQ 22708), a new vasodilator, in essential hypertension. Clin Exp Hypertens 4: 1409–1418
Kirch W, Axthelm T (1982) Endralazine, a new peripheral vasodilator — a randomized cross-over trial against dihydralazine. J Cardiovasc Pharmacol 4: 562–566
Reece PA, Cozamanis I, Zacest R (1981) A sensitive assay for endralazine and two of its metabolites in human plasma. J Chromatogr 225: 151–160
Reece PA, Cozamanis I, Zacest R (1981) Specific assay and initial pharmacokinetics of a new vasodilator antihypertensive endralazine. Clin Exp Pharmacol Physiol 8: 602
Reece PA, Cozamanis I, Zacest R (1981) Simultaneous pharmacokinetic and pharmacodynamic study of endralazine in healthy volunteers. I-Pharmacokinetics. Clin Exp Pharmacol Physiol 9: 477
Chapron DJ, Kramer PA, Mercik SA (1980) Kinetic discrimination of three sulfamethazine acetylation phenotypes. Clin Pharmacol Ther 27: 104–114
Jusko WJ (1981) Guidelines for collection and pharmacokinetic analysis of drug disposition data. In: Evans WE, Schentag JJ, Jusko WJ (eds) Applied pharmacokinetics. Applied therapeutics, San Francisco, USA
Reece PA, Cozamanis I, Zacest R (1980) Pharmacokinetics of hydralazine and its main metabolites in slow and fast acetylators. Clin Pharmacol Ther 28: 769–780
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Reece, P.A., Cozamanis, I. & Zacest, R. Influence of acetylator phenotype on the pharmacokinetics of a new vasodilator antihypertensive, endralazine. Eur J Clin Pharmacol 23, 523–527 (1982). https://doi.org/10.1007/BF00637500
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DOI: https://doi.org/10.1007/BF00637500