Mechanism by which hydralazine increases propranolol bioavailability

Journal Article · Sun Apr 01 04:00:00 EST 1984 · Clin. Pharmacol. Ther.; (United States)

DOI:https://doi.org/10.1038/clpt.1984.58· OSTI ID:6832879

Schneck, D W; Vary, J E

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), Journal Name: Clin. Pharmacol. Ther.; (United States) Vol. 35:4; ISSN CLPTA
• Country of Publication: United States
• Language: English

Related Subjects

551001* -- Physiological Systems-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANTIHYPERTENSIVE AGENTS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOLOGICAL AVAILABILITY
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BODY FLUIDS
CARBON 14 COMPOUNDS
CARDIOVASCULAR AGENTS
CLEARANCE
DRUGS
EXCRETION
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MATERIALS
SYMPATHOLYTICS
TRACER TECHNIQUES
URINE
WASTES