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Abstract

Antipyrine (AP) is a commonly used probe of oxidative metabolism. Indirect evidence demonstrates formation rate limited disposition of its metabolites. Kinetic studies using antipyrine and its major metabolites 3-hydroxymethylantipyrine (HMA), norantipyrine (NORA), and 4-hydroxyantipyrine (OHA) were completed to investigate the metabolic fate of preformed antipyrine metabolite and to demonstrate directly formation rate-limited metabolite disposition in vivo. Bolus injections of antipyrine and preformed metabolites (40-50 mg/kg) were administered to male, New Zealand white rabbits. Plasma and urine were analyzed using HPLC. These studies demonstrate that HMA, NORA, and OHA are formation rate limited in the rabbit. NORA appears to undergo further extensive oxidative and conjugative metabolism. Unknown additional peaks were detected in urine after NORA dosing but not after HMA or OHA administration. Mass spectroscopy of the unknown HPLC eluents identified potential structures of these NORA metabolites.

1,5-Dimethyl-2-phenyl-1H-pyrazol-3(2H)-one–4,4′-(propane-2,2-diyl)bis[1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one] (1/1)

“…For related structures, see: Singh & Vijayan (1973); Panneerselvam et al (1996); Merz (2002); Yuchi et al (1991). Some properties of antipyrine and its derivatives were described by Peter et al (1991). Symmetry codes: (i) Àx þ 3 2 ; y À 1 2 ; Àz þ 1 2 ; (ii) x þ 1; y þ 1; z; (iii) x À 1; y À 1; z; (iv) x; y þ 1; z. supporting information Acta Cryst.…”

“…Comment 1,5-Dimethyl-2-phenyl-1H-pyrazol-3(2H)-one, known as antipyrine or phenazone, is an interesting synthetic compound from the medicinal (pharmaceutical) point of view because of its analgesic and antipyretic properties. It is also used as a probe of oxidative metabolism (Peter et al, 1991). Antipyrine is a bulky monodentate donor ligand.…”