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  • Title: Plasma kinetics of dipyrone metabolites in rapid and slow acetylators.
    Author: Levy M, Flusser D, Zylber-Katz E, Granit L.
    Journal: Eur J Clin Pharmacol; 1984; 27(4):453-8. PubMed ID: 6519153.
    Abstract:
    The pharmacokinetics of the dipyrone metabolites 4-methylaminoantipyrine (MAA), 4-aminoantipyrine (AA), 4-formylaminoantipyrine (FAA) and 4-acetylaminoantipyrine (AAA) were evaluated following the administration of a single oral 1.0 g dose of dipyrone to 23 healthy volunteers. Twelve were slow and 11 were rapid acetylators as previously determined by dapsone phenotyping. For MAA and FAA the mean peak plasma concentrations were 10.5 +/- 2.8 micrograms/ml and 2.1 +/- 0.8 micrograms/ml and the half-lives were 3.3 +/- 1.0 and 10.1 +/- 1.8 h, respectively. No significant difference was found between rapid and slow acetylators in MAA and FAA kinetics. For AA, the mean peak plasma concentrations were 2.7 +/- 0.6 and 1.6 +/- 0.7 micrograms/ml (p less than 0.01), the peak times 6.7 +/- 2.1 and 3.1 +/- 1.1 h (p less than 0.01) and the half-lives were 5.5 +/- 1.0 and 3.8 +/- 1.2 h in slow and rapid acetylators, respectively. For AAA, the mean peak plasma concentrations were 1.6 +/- 0.4 and 4.4 +/- 1.1 micrograms/ml (p less than 0.01) and the peak time 16.1 +/- 5.1 and 10.0 +/- 2.6 h (p less than 0.01) in slow and rapid acetylators, respectively. There was no difference in the elimination half-life between the two groups (10.6 +/- 2.2 h). Thus, it has been demonstrated that the AAA/AA ratio is an indicator of the acetylation phenotype, as it is closely correlated with that determined by dapsone (r = 0.895, p less than 0.0005).
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