Summary
The formation and urinary excretion of the dipyrone metabolites, methylaminoantipyrine (MAA), aminoantipyrine (AA), formylaminoantipyrine (FAA) and acetylaminoantipyrine (AAA) were determined following administration of a single oral 1.0 g dose of dipyrone to 12 healthy volunteers. The AAA/AA plasma ratio showed that 3 subjects were slow and 9 were rapid acetylators. Pharmacokinetic parameters were determined separately for each group.
A good correlation was found between the plasma and urine AAA/AA ratios. The renal clearance of the four metabolites was similar for both phenotypes. A significant difference in the rate of formation of dipyrone metabolites was found for AA, 0.25 (slow) vs 0.1 ml·min−1·kg−1 (rapid), and for AAA 0.75 (slow) vs 7.53 ml·min−1·kg−1 (rapid). There were comparable differences between slow and rapid acetylators in the AUC and the urinary excretion extrapolated to infinity for AA and AAA.
The present results show that the kinetics of dipyrone metabolites in plasma and urine can provide a useful measure of the activity of the enzymes involved in their production.
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References
Volz M, Kellner HM (1980) Kinetics and metabolism of pyrazolones (propyphenazone, aminopyrine and dipyrone). Br J Clin Pharmacol 10 [Suppl 2]: 299–308
Levy M, Flusser D, Zylber-Katz E, Granit L (1984) Plasma kinetics of dipyrone metabolites in rapid and slow acetylators. Eur J Clin Pharmacol 27: 453–458
Zylber-Katz E, Granit L, Drayer DE, Levy M (1984) Simultaneous determination of dipyrone metabolites in plasma by high-performance liquid chromatography. J Chromatogr 305: 477–484
Boobis AR, Brodie MJ, Kahn CC, Toverud EL, Blair IA, Murray S, Davies DS (1981) Comparison of the in vivo and in vitro rates of formation of the three main oxidative metabolites of antipyrine in man. Br J Clin Pharmacol 12: 771–777
Zylber-Katz E, Granit L, Levy M (1985) Plasma protein binding of dipyrone metabolites in man. Eur J Clin Pharmacol 29: 67–71
Christ O, Kellner HM, Ross C, Rupp W, Schwarz A (1973) Biopharmazeutische und Pharmakokinetische Untersuchungen nach Gabe von Metamizol 14C an Ratte, Hund und Mensch. Arzneimittelforschung 23: 1760–1767
Flusser D, Zylber-Katz E, Granit L, Levy M (1988) Influence of food on the pharmacokinetics of dipyrone. Eur J Clin Pharmacol 34: 105–107
Zylber-Katz E, Granit L, Stessman J, Levy M (1989) Effect of age on the pharmacokinetics of dipyrone. Eur J Clin Pharmacol 36: 513–516
The International Agranulocytosis and Aplastic Anemia Study (1986) Risks of agranulocytosis and aplastic anemia. A first report of their relation to drug use with special reference to analgesics. JAMA 256: 1749–1757
Arellano F, Sacristan SA (1990) Metamizole: Reassessment of its therapeutic role. Eur J Clin Pharmacol 38: 617–619
Roots I, Kampf D, Heinemeyer G, Gramm HS, Dennhardt R (1985) Changes in metamizol kinetics and metabolism during chronic and acute renal failure as compared to healthy volunteers. Naunyn-Schmiedeberg's Arch Pharmacol 330: R 81
Perrier D, Gibaldi M (1974) Clearance and biologic half-life as indices of intrinsic hepatic metabolism. J Pharmacol Exp Ther 191: 17–24
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Zylber-Katz, E., Granit, L. & Levy, M. Formation and excretion of dipyrone metabolites in man. Eur J Clin Pharmacol 42, 187–191 (1992). https://doi.org/10.1007/BF00278482
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DOI: https://doi.org/10.1007/BF00278482