Impairment of the metabolism of dipyrone in asymptomatic carriers of the hepatitis-B virus does not occur in rapid acetylators

Objective: We previously found that, compared with healthy subjects, asympt omatic hepatitis-B virus (HBV) carriers displaying slow acetylator phenotyp e demonstrate a significant prolongation of the elimination half-life of 4- methylaminoantipyrine (MAA) and a decrease in the clearance of formation of 4-aminoantipyrine (AA) and 4-formylaminoantipyrine (FAA). However, the for mation of 4-acetylaminoantipyrine (AAA) was unchanged. The present study wa s designed to examine the effect of the asymptomatic HBV carrier state on t he metabolism of dipyrone, as a model drug, in rapid acetylators. Methods: The plasma and urine concentrations of the metabolites of dipyrone were measured in eight asymptomatic HBV carriers and eight healthy subject s who had normal liver function tests, all displaying the rapid acetylation phenotype and genotype, after the administration of a 1.0-g oral dose of d ipyrone. Results: The following pharmacokinetic parameters were evaluated: peak plas ma concentration, time to peak plasma concentration, elimination rate const ant, area under the plasma concentration-time curve (0 --> infinity), amoun t excreted (0 --> infinity), renal and non-renal clearances for MAA and the clearances of formation for AA, FAA and AAA. No significant differences we re found between the two subject groups. Conclusion: The effect of hepatic viral carrier state on drug metabolism ma y vary according to metabolic pathways and genetic polymorphism.