Disease relevance of NSC174055

• 1 The metabolism of antipyrine to its three main oxidative metabolites, 4-hydroxyantipyrine, 3-hydroxymethylantipyrine and norphenazone was investigated in vivo and in vitro in separate groups of subjects with normal hepatic function and in the same group of patients with suspected liver disease [1].

High impact information on NSC174055

• Furthermore, the data also indicated a good negative correlation between AHH inducibility and the measurements of plasma antipyrine or urinary 4-hydroxyantipyrine half-lives (r = -0.88 or -0.91), respectively [2].
• Antibodies against CYP3A4 inhibited the formation of 4-hydroxyantipyrine by 25% to 65% [3].
• RESULTS: Antipyrine biotransformation could be described by Michaelis-Menten kinetics: norantipyrine: maximum rate of metabolite formation (Vmax), 0.91 +/- 0.04 nmol . mg-1 . min-1; Michaelis-Menten constant (Km), 19.0 +/- 0.8 mmol/L; 4-hydroxyantipyrine: Vmax, 1.54 +/- 0.08 nmol . mg-1 . min-1;Km,39.6 +/- 2.5 mmol/L [3].
• To evaluate the role of antipyrine as a model drug, we have identified the cytochrome P450 enzymes involved in 4-hydroxyantipyrine, 3-hydroxymethylantipyrine, and norantipyrine formation [3].
• Studies have indicated that more than one P450 is involved in the formation of the three major human metabolites, 4-hydroxyantipyrine, norantipyrine, and 3-hydroxymethylantipyrine [4].

Biological context of NSC174055

• The biotransformation of a relatively polar and only slightly plasma protein-bound drug, antipyrine, was subject to product inhibition by a hydroxylated metabolite, 4-hydroxyantipyrine [5].
• This inhibitory effect makes it impossible to perform a global assay of antipyrine metabolites after enzymatic or chemical hydrolysis and confirms the value of direct assay of the 4-hydroxyantipyrine sulphoconjugate [6].
• 1 The influence of enzyme induction with antipyrine and pentobarbitone was studied on the rates of formation of the major metabolites of antipyrine: 4-hydroxyantipyrine, norantipyrine and 3-hydroxymethyl-antipyrine + 3-carboxy-antipyrine [7].
• The pharmacokinetics of antipyrine were determined on the basis of the saliva concentration time curve and the cumulative urinary excretion of 4-hydroxyantipyrine, norantipyrine, 3-hydroxymethyl-antipyrine, and 3-carboxyantipyrine was measured for 32 h following drug administration [8].

Anatomical context of NSC174055

• The intrinsic clearance values for production of 3-hydroxymethyl-, nor- and 4-hydroxyantipyrine were 232 (43-519) and 487 (296-793; P less than 0.05), 594 (168-813) and 93 (55-180; P less than 0.05), and 118 (23-505) and 239 (134-501; P greater than 0.05) nl/min per 10(6) hepatocytes, for mouse and rat, respectively (median with range, n = 6) [9].

Associations of NSC174055 with other chemical compounds

• The glucuronide conjugates of the two isomeric antipyrine phase I metabolites of antipyrine in man, 4-hydroxyantipyrine and 3-hydroxymethylantipyrine have been analysed by field desorption and fast atom bombardment mass spectrometry [10].

Analytical, diagnostic and therapeutic context of NSC174055

• A high-performance liquid chromatography method is described which allows for the simultaneous determination of antipyrine, 4-hydroxyantipyrine, norantipyrine and 3-hydroxyantipyrine [11].
• After treatment 4-hydroxyantipyrine was increased from 13.4% to 25.6% dose, whereas 3-hydroxymethylantipyrine was decreased from 26.8% to 8.5% and 3-carboxyantipyrine from 1.3% to 0.2% of the dose respectively; norantipyrine was unchanged [12].
• The concentrations of antipyrine, 4-hydroxyantipyrine (4-OHA), 3-hydroxymethylantipyrine (HMA) and norantipyrine (NORA) were measured in plasma and urine by high performance liquid chromatography (HPLC) [13].

References