Impairment of antipyrine clearance in humans by propranolol
| Autor: | Kate Franke, David J. Greenblatt, David H. Huffman |
|---|---|
| Rok vydání: | 1978 |
| Předmět: |
Adult
Male Drug Metabolite media_common.quotation_subject Propranolol Pharmacology Hydroxylation chemistry.chemical_compound Physiology (medical) Humans Medicine media_common Volume of distribution business.industry Half-life Blood flow Blockade chemistry Female Cardiology and Cardiovascular Medicine business Antipyrine Half-Life medicine.drug |
| Zdroj: | Circulation. 57:1161-1164 |
| ISSN: | 1524-4539 0009-7322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|