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Impairment of the metabolism of dipyrone in asymptomatic carriers of the hepatitis B virus
Author(s) -
Levy Micha,
Leibowich Igal,
ZylberKatz Ester,
Ilan Yaron,
Granit Liora,
Sviri Sigal,
Caraco Yoseph
Publication year - 1997
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(97)90145-4
Subject(s) - pharmacokinetics , medicine , asymptomatic , asymptomatic carrier , metabolite , gastroenterology , virus , liver disease , hepatitis , pharmacology , immunology
Background The pharmacokinetics of a number of drugs has been shown to be impaired in patients with acute or chronic viral liver disease. Objective To examine the effect of the asymptomatic hepatitis B virus carrier state on the metabolism of dipyrone (INN, metamizole) as a model drug. Methods The pharmacokinetics of the metabolites of dipyrone—4‐methylaminoantipyrine, 4‐aminoantipyrine, 4‐formylaminoantipyrine, and 4‐acetylaminoantipyrine—after a 1.0 gm oral dose of dipyrone were evaluated in nine asymptomatic carriers of hepatitis B virus with normal liver function tests and nine healthy subjects. All subjects displayed the slow acetylator phenotype. Results The nonrenal (metabolic) clearance 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 healthy subjects, and the elimination half‐life of this metabolite was significantly longer (3.69 ± 0.35 versus 2.64 ± 0.28 hours, respectively; p < 0.03). The formation clearances of 4‐aminoantipyrine and 4‐formylaminoantipyrine were significantly smaller in the carriers of hepatitis 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 the carriers of hepatitis B virus. No significant differences were noted between the groups in the pharmacokinetics of 4‐acetylaminoantipyrine. Conclusion The metabolism of dipyrone is impaired in asymptomatic carriers of hepatitis B virus. Clinically latent infection with hepatitis B virus seems to exert a differential effect on metabolism of the drug. Oxidative pathways to produce 4‐aminoantipyrine and 4‐formylaminoantipyrine were significantly affected, whereas acetylation remained intact. This study provided an additional example of the effect of a virus on the disposition of a drug. Clinical Pharmacology & Therapeutics (1997) 62 , 6–14; doi: