Abstract
1 The metabolism of paracetamol after a single oral dose of 20 mg/kg was compared in fifteen patients with microsomal enzyme induction taking anticonvulsants or rifampicin and twelve healthy volunteers. 2 Induction was confirmed by measurement of the plasma antipyrine half-life (mean 6.4 h in the patients compared with 12.8 h in the volunteers). 3 The glucuronide conjugation of paracetamol was enhanced in the induced patients as shown by lower plasma paracetamol concentrations, a shorter paracetamol half-life, higher paracetamol glucuronide concentrations and an increased ratio of the area under the plasma concentration time curves of the glucuronide to the unchanged drug. There were no significant differences in sulphate conjugation. 4 There was a corresponding change in the pattern of urinary metabolite excretion. The induced patients excreted significantly less unchanged drug and sulphate conjugate and more glucuronide conjugate than the healthy volunteers. 5 The urinary excretion of the mercapturic acid and cysteine conjugated of paracetamol was the same in both groups. 6 Conversion of paracetamol to its potentially hepatotoxic metabolite does not seem to be increased in patients induced with anticonvulsants or rifampicin. There would seem to be no contraindication to the use of these drugs in combination.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Adriaenssens P. I., Prescott L. F. High performance liquid chromatographic estimation of paracetamol metabolites in plasma. Br J Clin Pharmacol. 1978 Jul;6(1):87–88. doi: 10.1111/j.1365-2125.1978.tb01687.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gerber M. A., Kaufmann H., Klion F., Alpert L. I. Acetaminophen associated hepatic injury, Report of two cases showing unusual portal tract reactions. Hum Pathol. 1980 Jan;11(1):37–42. doi: 10.1016/s0046-8177(80)80103-1. [DOI] [PubMed] [Google Scholar]
- Goldfinger R., Ahmed K. S., Pitchumoni C. S., Weseley S. A. Concomitant alcohol and drug abuse enhancing acetaminophen toxicity. Report of a case. Am J Gastroenterol. 1978 Oct;70(4):385–388. [PubMed] [Google Scholar]
- Jollow D. J., Thorgeirsson S. S., Potter W. Z., Hashimoto M., Mitchell J. R. Acetaminophen-induced hepatic necrosis. VI. Metabolic disposition of toxic and nontoxic doses of acetaminophen. Pharmacology. 1974;12(4-5):251–271. doi: 10.1159/000136547. [DOI] [PubMed] [Google Scholar]
- Licht H., Seeff L. B., Zimmerman H. J. Apparent potentiation of acetaminophen hepatotoxicity by alcohol. Ann Intern Med. 1980 Apr;92(4):511–511. doi: 10.7326/0003-4819-92-4-511_1. [DOI] [PubMed] [Google Scholar]
- McClain C. J., Kromhout J. P., Peterson F. J., Holtzman J. L. Potentiation of acetaminophen hepatotoxicity by alcohol. JAMA. 1980 Jul 18;244(3):251–253. [PubMed] [Google Scholar]
- Mitchell J. R., Jollow D. J., Potter W. Z., Davis D. C., Gillette J. R., Brodie B. B. Acetaminophen-induced hepatic necrosis. I. Role of drug metabolism. J Pharmacol Exp Ther. 1973 Oct;187(1):185–194. [PubMed] [Google Scholar]
- Mitchell J. R., Thorgeirsson S. S., Potter W. Z., Jollow D. J., Keiser H. Acetaminophen-induced hepatic injury: protective role of glutathione in man and rationale for therapy. Clin Pharmacol Ther. 1974 Oct;16(4):676–684. doi: 10.1002/cpt1974164676. [DOI] [PubMed] [Google Scholar]
- Perucca E., Richens A. Paracetamol disposition in normal subjects and in patients treated with antiepileptic drugs. Br J Clin Pharmacol. 1979 Feb;7(2):201–206. doi: 10.1111/j.1365-2125.1979.tb00922.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Streeter A. J., Timbrell J. A. The effect of dichloralphenazone pretreatment on paracetamol hepatotoxicity in mice. Biochem Pharmacol. 1979 Oct 1;28(19):3035–3037. doi: 10.1016/0006-2952(79)90609-9. [DOI] [PubMed] [Google Scholar]
- Strubelt O., Obermeier F., Siegers C. P. The influence of ethanol pretreatment on the effects of nine hepatotoxic agents. Acta Pharmacol Toxicol (Copenh) 1978 Sep;43(3):211–218. doi: 10.1111/j.1600-0773.1978.tb02257.x. [DOI] [PubMed] [Google Scholar]
- Teschke R., Stutz G., Strohmeyer G. Increased paracetamol-induced hepatotoxicity after chronic alcohol consumption. Biochem Biophys Res Commun. 1979 Nov 14;91(1):368–374. doi: 10.1016/0006-291x(79)90628-4. [DOI] [PubMed] [Google Scholar]
- Wrights N., Prescott L. F. Potentiation by previous drug therapy of hepatotoxicity following paracetamol overdosage. Scott Med J. 1973 Mar;18(2):56–58. doi: 10.1177/003693307301800205. [DOI] [PubMed] [Google Scholar]