Effect of oral dose size on hydralazine kinetics and vasodepressor response

Alexander M.M. Shepherd, Norman A. Irvine, Thomas M. Ludden, Min Shung Lin, John L. McNay

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Levels of hydralazine in blood are log-linearly related to its vasodepressor effect. We examined the effect of oral dose size on the proportion of hydralazine that reaches systemic circulation. Nine subjects with hypertension were given hydralazine in oral doses in the therapeutic range. Blood hydralazine levels, effective liver blood flow, blood pressure, and heart rate were measured. As the hydralazine dose increased, the ratios of the AUC of hydralazine to hydralazine dose and of peak blood hydralazine concentration to hydralazine dose increased, indicating an increase in the proportion of the dose in blood. Liver blood flow tended to increase (maximum 40%) as dose increased above 0.5 mg/kg Vasodepressor response and degree of tachyeardia increased disproportionately with increasing hydralazine dose. There were strong log-linear relationships between peak hydralazine levels and both vasodepressor response and tachyeardia that did not change with increasing hydralazine dose. Thus blood hydralazine and vasodepressor response increase disproportionately with increasing hydralazine doses in hypertension.

Original languageEnglish (US)
Pages (from-to)595-600
Number of pages6
JournalClinical Pharmacology and Therapeutics
Volume36
Issue number5
DOIs
StatePublished - Nov 1984

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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