IMPAIRMENT OF THE METABOLISM OF DIPYRONE IN ASYMPTOMATIC CARRIERS OF THE HEPATITIS-B VIRUS

Background: The pharmacokinetics of a number of drugs has been shown t o be impaired in patients with acute or chronic viral liver disease. O bjective: To examine the effect of the asymptomatic hepatitis B virus carrier state on the metabolism of dipyrone (INN, metamizole) as a mod el drug. Methods: The pharmacokinetics of the metabolites of dipyrone- 4-methylaminoantipyrine, 4-aminoantipyrine, 4-formylaminoantipyrine, a nd 4-acetylaminoantipyrine-after a 1.0 gm oral dose of dipyrone were e valuated in nine asymptomatic carriers of hepatitis B virus with norma l Liver function tests and nine healthy subjects. All subjects display ed the slow acetylator phenotype. Results: The nonrenal (metabolic) cl earance of 4-methylaminoantipyrine was significantly reduced (mean +/- SEM) (123.3 +/- 15.8 versus 182.9 +/- 15.1 ml . min(-1), respectively ; p < 0.02) in the carriers of hepatitis B virus compared with the hea lthy subjects, and the elimination half-life of this metabolite was si gnificantly longer (3.69 +/- 0.35 versus 2.64 +/- 0.28 hours, respecti vely; p < 0.03), The formation clearances of 4-aminoantipyrine and 4-f ormylaminoantipyrine were significantly smaller in the carriers of hep atitis B virus compared with healthy subjects (33.8 +/- 6.2 versus 55. 2 +/- 6.4 ml . min(-1); p < 0.03, and 16.7 +/- 2.2 versus 34.2 +/- 4.2 ml . min(-1); p < 0.002, respectively), However, the elimination half -life of 4-formylaminoantipyrine was found to be slightly shorter in t he carriers of hepatitis B virus, No significant differences were note d between the groups in the pharmacokinetics of 4-acetylaminoantipyrin e. Conclusion: The metabolism of dipyrone is impaired in asymptomatic carriers of hepatitis B virus, Clinically latent infection with hepati tis B virus seems to exert a differential effect on metabolism of the drug, Oxidative pathways to produce 4-aminoantipyrine and 4-formylamin oantipyrine were significantly affected, whereas acetylation remained intact. This study provided an additional example of the effect of a v irus on the disposition of a drug.