Impairment of antipyrine clearance in humans by propranolol.
- 1 June 1978
- journal article
- research article
- Published by Wolters Kluwer Health in Circulation
- Vol. 57 (6), 1161-1164
- https://doi.org/10.1161/01.cir.57.6.1161
Abstract
The effect of propranolol on antipyrine clearance in humans was evaluated in six healthy volunteers who received single 1.4 to 1.5 g doses of intravenous antipyrine on two occasions. The first (control) antipyrine trial was without concurrent drug administration; the second trial was done during treatment with therapeutic doses of propranolol (40 mg every 4 to 6 hours). Antipyrine elimination half-life (t1/2), volume of distribution (Vd), and total clearance were determined after each trial. In all subjects isoproterenol sensitivity decreased markedly during propranolol treatment, indicating a high degree of beta blockade produced by the drug. Mean antipyrine t1/2 during the propranolol treatment period was significantly prolonged, and total clearance significantly reduced, over the control values. Twenty-four-hour urinary excretion of 4-hydroxyantipyrine, the major metabolite of antipyrine, likewise was reduced from 23.6% of the dose on the control trial to 14.8% of the dose during propranolol coadministration (0.1 less than P less than 0.2). Vd however, was nearly identical during both trials (0.62 L/kg). Thus propranolol prolongs the half-life and reduces the clearance or biotransformation rate of antipyrine, a drug whose clearance is independent of hepatic blood flow. Propranolol may influence the activity of hepatic microsomal enzymes responsible for drug hydroxylation.This publication has 15 references indexed in Scilit:
- Factors influencing antipyrine elimination.British Journal of Clinical Pharmacology, 1977
- Clinical PharmacokineticsNew England Journal of Medicine, 1975
- Studies on the disposition of antipyrine, aminopyrine, and phenacetin using plasma, saliva, and urineClinical Pharmacology & Therapeutics, 1975
- Effeets of etiocholanolone‐indueed fever on plasma antipyrine half‐lives and metabolie elearaneeClinical Pharmacology & Therapeutics, 1975
- Comparison of plasma levels of antipyrine, tolbutamide, and warfarin after oral and intravenous administrationClinical Pharmacology & Therapeutics, 1974
- Change in d-glucaric excertion in relationship to alterations in the rate of antipyrine metabolism in manBiochemical Pharmacology, 1974
- Correlation of the plasma elimination of antipyrine and the appearance of 4-hydroxy antipyrine in the urine of manBiochemical Pharmacology, 1974
- Relationship between Plasma Antipyrine Half-Lives and Hepatic Microsomal Drug Metabolism in DogsPharmacology, 1973
- A Standardized Isoproterenol Sensitivity TestArchives of Internal Medicine, 1972
- Genetic control of the phenobarbital-induced shortening of plasma antipyrine half-lives in manJCI Insight, 1969