Abstract
1. In a previous study in rats, an increased PAH clearance was found following chronic phenobarbitone administration. These results formed the basis for the present study in which fifteen healthy male volunteers were investigated and the parameters of liver microsomal enzyme activity and renal function were measured. 2. As parameters of liver microsomal enzyme activity, the antipyrine elimination in the plasma, the gamma-glutamyl-transpeptidase and the D-glucaric excretion in the urine were measured. Endogenous creatinine clearance, 51Cr-EDTA and 125I-Hippuran clearance were determined as measurements of renal function. 3. No correlation was found between any of the parameters of microsomal enzyme activity and renal function. 4. Of the fifteen volunteers, seven having a mean antipyrine half-life of 13.3 h were given antipyrine (500 mg) daily for 3 weeks. Afterwards all measurements of liver microsomal enzyme activity and renal function were repeated. The antipyrine half-life decreased to 8.5 h, while the antipyrine clearance was increased by about 56%. gamma-glutamyl-transpeptidase and D-glucaric acid were also significantly increased, while renal function remained unchanged. 5. Therefore, an increased PAH-clearance, as found in the rat, is not obtained in man following induction of liver microsomal enzyme activity.
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Selected References
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- Branch R. A., Shand D. G., Wilkinson G. R., Nies A. S. Increased clearance of antipyrine and d-propranolol after phenobarbital treatment in the monkey. Relative contributions of enzyme induction and increased hepatic blood flow. J Clin Invest. 1974 Apr;53(4):1101–1107. doi: 10.1172/JCI107647. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Breckenridge A., Orme M. L., Davies L., Thorgeirsson S. S., Davies D. S. Dose-dependent enzyme induction. Clin Pharmacol Ther. 1973 Jul-Aug;14(4):514–520. doi: 10.1002/cpt1973144part1514. [DOI] [PubMed] [Google Scholar]
- Feuer G., Sosa-Lucero J. C., Lumb G., Moddel G. Failure of various drugs to induce drug-metabolizing enzymes in extrahepatic tissues of the rat. Toxicol Appl Pharmacol. 1971 Aug;19(4):579–589. doi: 10.1016/0041-008x(71)90290-0. [DOI] [PubMed] [Google Scholar]
- Hildebrandt A. G., Roots I., Speck M., Saalfrank K., Kewitz H. Evaluation of in vivo parameters of drug metabolizing enzyme activity in man after administration of clemastine, phenobarbital or placebo. Eur J Clin Pharmacol. 1975 Jun 13;8(5):327–336. doi: 10.1007/BF00562658. [DOI] [PubMed] [Google Scholar]
- Jakobsson S., Thor H., Orrenius S. Fatty acid inducible cy tochrome P-454 of rat kidney cortex microsomes. Biochem Biophys Res Commun. 1970;39(6):1073–1080. doi: 10.1016/0006-291x(70)90668-6. [DOI] [PubMed] [Google Scholar]
- March J., Turner W. J., Shanley J., Field J. Values for urinary excretion of D-glucaric acid by normal individuals. Clin Chem. 1974 Sep;20(9):1155–1158. [PubMed] [Google Scholar]
- Marsh C. A. Metabolism of d-glucuronolactone in mammalian systems. Identification of d-glucaric acid as a normal constituent of urine. Biochem J. 1963 Jan;86(1):77–86. doi: 10.1042/bj0860077. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ohnhaus E. E., Thorgeirsson S. S., Davies D. S., Breckenridge A. Changes in liver blood flow during enzyme induction. Biochem Pharmacol. 1971 Oct;20(10):2561–2570. doi: 10.1016/0006-2952(71)90164-x. [DOI] [PubMed] [Google Scholar]
- Ohnhaus E. E. Urinary excretion of chlorothiazide in rats before and after phenobarbitone administration. Experientia. 1972 Jul 15;28(7):821–822. doi: 10.1007/BF01923152. [DOI] [PubMed] [Google Scholar]
- Orme M. L., Davies L., Breckenridge A. Increased glucuronidation of bilirubin in man and rat by administration of antipyrine (phenazone). Clin Sci Mol Med. 1974 Apr;46(4):511–518. doi: 10.1042/cs0460511. [DOI] [PubMed] [Google Scholar]
- Prescott L. F. Pharmacokinetic drug interactions. Lancet. 1969 Dec 6;2(7632):1239–1243. doi: 10.1016/s0140-6736(69)90766-1. [DOI] [PubMed] [Google Scholar]
- SAPIRSTEIN L. A., VIDT D. G., MANDEL M. J., HANUSEK G. Volumes of distribution and clearances of intravenously injected creatinine in the dog. Am J Physiol. 1955 May;181(2):330–336. doi: 10.1152/ajplegacy.1955.181.2.330. [DOI] [PubMed] [Google Scholar]
- Storch R., Bräunlich H. Stimulation der renalen Ausscheidung von p-Aminohippursäure durch Wiederholte Applikation von Phenobarbital. Acta Biol Med Ger. 1975;34(3):519–521. [PubMed] [Google Scholar]
- Szasz G. A kinetic photometric method for serum gamma-glutamyl transpeptidase. Clin Chem. 1969 Feb;15(2):124–136. [PubMed] [Google Scholar]
- Tauxe W. N., Maher F. T., Taylor W. F. Effective renal plasma flow: estimation from theoretical volumes of distribution of intravenously injected 131-I orthoiodohippurate. Mayo Clin Proc. 1971 Aug;46(8):524–531. [PubMed] [Google Scholar]
- Truniger B., Donath A., Kappeler M. Simplified clearance techniques. The single injection method and its modifications. Helv Med Acta. 1968 Mar;34(2):116–129. [PubMed] [Google Scholar]
- Whitfield J. B., Moss D. W., Neale G., Orme M., Breckenridge A. Changes in plasma -glutamyl transpeptidase activity associated with alterations in drug metabolism in man. Br Med J. 1973 Feb 10;1(5849):316–318. doi: 10.1136/bmj.1.5849.316. [DOI] [PMC free article] [PubMed] [Google Scholar]