Mechanism by which hydralazine increases propranolol bioavailability
Five healthy subjects were given oral /sup 14/C-propranolol (10 microCi, 40 mg) alone and in combination with hydralazine, 25 and 50 mg. Hydralazine increased propranolol peak concentrations from 25 +/- 7 ng/ml to 61 +/- 10 and 85 +/- 11 ng/ml, reduced time to peak concentrations from 2.2 +/- 0.2 hr to 0.7 +/- 0.1 and 0.8 +/- 0.1 hr, and increased area under the propranolol concentration: time curves from 153 +/- 38 ng X ml-1 X hr to 246 +/- 64 and 324 ng X ml-1 X hr (in all cases P less than 0.05). Hydralazine did not change the fraction of the /sup 14/C-propranolol dose recovered in the urine as basic, acidic, and polar metabolites: 0.28 +/- 0.2, 0.27 +/- 0.03, and 0.44 +/- 0.03. The urinary excretion rate of radioactive metabolites of propranolol in acid, basic, and residue fractions increased in the 0 . to . 2-hr time interval after hydralazine but there was no change in the relative proportion of each metabolite fraction at any time. Similar results were obtained by HPLC. Studies with radioactive propranolol indicate that a major acid and basic metabolite remains to be defined in addition to unextracted polar metabolites. Our data indicate that hydralazine increases propranolol bioavailability by its hemodynamic actions rather than by inhibition of its metabolism.
- Research Organization:
- Hershey, Department of Medicine, Pennsylvania State University College of Medicine
- OSTI ID:
- 6832879
- Journal Information:
- Clin. Pharmacol. Ther.; (United States), Vol. 35:4
- Country of Publication:
- United States
- Language:
- English
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CARBON 14 COMPOUNDS
EXCRETION
TRACER TECHNIQUES
URINE
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
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551001* - Physiological Systems- Tracer Techniques