Antipyrine test

Neuvonen PJ, Tokola RA, Kaste M. Cimetidine-phenytoin interaction effect on serum phenytoin concentration and antipyrine test. Eur J Clin Pharmacol 1981 21(3) 215-20. 

Knorr reported the first pyrazole derivative in 1883. The reaction of phenyl hydrazine and ethylacetoacetate resulted in a novel stmcture identified in 1887 as l-phenyl-3-methy 1-5-pyrazolone 9. His interest in antipyretic compounds led him to test these derivatives for antipyretic activity which led to the discovery of antipyrine 10. He introduced the name pyrazole for these compounds to denote that the nucleus was derived from the pyrrole by replacement of a carbon with a nitrogen. He subsequnently prepared many pyrazole analogs, particularly compounds derived from the readily available phenyl hydrazine. The unsubstituted pyrazole wasn t prepared until 1889 by decarboxylation of liT-pyrazole-3,4,5-tricarboxylic acid. ... 

Uptake and Elimination. Six mussels were placed into 600 ml beakers containing 300 ml aerated Instant 0ceanR (10-12°C) for a 1/2 hr acclimation period before addition of antipyrine (3 pCi/ beaker) (or other test compound). Aliquots (1.0 ml) were taken at intervals and placed directly into scintillation fluid (10 ml, 3a70B, Research Products International Corp., Elk Grove Village,... 

Quantitative estimation of ventilation by indirect methods in mussels requires four assumptions (16) a) reduction of concentration results from uptake, b) constant ventilation (pumping) rate, c) uptake of a constant percentage of concentration (first order process), d) homogeneity of the test solution at all times. Our transport studies have utilized antipy-rine (22, 23) a water soluble, stable chemical of low acute toxicity to mussels. It is readily dissolved in ocean water or Instant Ocean and is neither adsorbed nor volatilized from the 300 ml test system. Mussels pump throughout the 4 hour test period and this action is apparently sufficient to insure homogeneity of the solution. Inspection of early uptake and elimination curves (antipyrine concentration as a function of time) prompted use of Coughlan s equation (16) for water transport. 

These studies with aldrin and antipyrine are sufficient to document the in vivo oxidative metabolic capability of mussels. Limits of activity have not been established, but they will be explored by further varying dose and the duration of the test period. With these limits established, the influence of environmental stressors such as salinity, and dissolved and/or suspended particulate matter in water on biotransformation will be assessed. If biotransformation processes are affected by these conditions, their measurement may provide results which can be diagnostically used as indicators of environmental quality. 

The structural feature of aminopyrine is similar to antipyrine except that aminopyrine has a substituent (dimethylamino group) at the C-4 position (Fig. 4). The exceptional efficacy of the aminopyrine breath test derives from the presence of multiple N-methyl groups that are readily removed by oxidative N-demethyla-tion. Hence, further oxidation of several formaldehyde molecules produced by demethylation of aminopyrine gives large volumes of labeled COj that is readily quantified. Some of the metabohtes of aminopyrine are given in Fig. 4 [30, 85, 87-90]. 

Santoni et al. have developed and used an ultraviolet spectroscopic method for the simultaneous assay of procaine and antipyrine [34]. The method allowed for a rapid and accurate determination of such mixtures over the tested concentration range of 2-9 pg/mL for procaine. 

Klebovitch I, Rautio A, Salonpaa et al. (1995) Antipyrine, coumarin and glipizide affect N-acetylation measured by caffeine test. Biomedicine and Pharmacotherapy 49 225-227... 

Coverdale SA, Samarasinghe DA, Lin R, et al. (2003) Changes in antipyrine clearance and platelet count, but not conventional liver tests, correlate with fibrotic change in chronic hepatitis C value for predicting fibrotic progression. Am J Gastroenterol 98 1384—1390. 

FIGURE 7.4 Relationship between Child-Pugh stages of liver disease severity and extent of impairment in antipyrine breath test (ABT), galactose elimination capacity (GEC), sorbitol clearance, and indocyanine green clearance (ICG). (Adapted from data published by Herold C, Heinz R, Niedobitek G et al. Liver 2001 21 260-5.)... 

Phenazone, commonly known as antipyrine, is still used therapeutically in some countries, although it is now used mainly as a marker of hepatic enzyme drug metabolizing activity. It is an old compound with little recent investigation, usually taken in combination with other analgesics, and an exact analysis of its adverse effects is impossible. Phenazone seems to have a low toxicity index, in correspondence with its weak anti-inflammatory effect. Allergic reactions are very rare (SEDA-6, 92) (SEDA-14, 92) (SEDA-16,108), but subjects undergoing the phenazone test should be informed of the potential risk. 

Methods that involve studying the disposition of some exogenously administered agent (e.g. indocyanine green, antipyrine, galactose or dextromethorphan) have now been superceded by functional (often multicomponent) tests. Mono-ethylglycinexylidide formation has not found wide acceptance. More complicated Cox proportional hazards models may exist for other liver diseases, but are only used specifically for them (e.g. the Mayo Clinic Survival Model for primary biliary cirrhosis see the US FDA Guidance). 

Clearance of antipyrine, a known substrate for microsomal hepatic enzymes, was used to test liver function in two studies of PCB-exposed workers (Alvares et al. 1977 Emmett et al. 1988b). A significantly lower mean half-life of antipyrine clearance from blood was found in five workers exposed... 

Compounds ofher fhan phenols are also capable of giving color reactions with iron(III). Of special inferesf are fhe ones forming red or violet complexes formate and acetate, benzoate, acetylacetone, and antipyrine. Even some steroids can give red complexes with iron(lll) through enolization of a carbonyl group.Selectivity in the test method is given by the color of fhe complex and its stability even after adding acetic acid. 

Different approaches have been used for the hydrosilylation of allylglycosides with various H-functional polysiloxanes [71, 78, 85-87], Glucopyranosyl- and cellobiosyl-terminated oligodimethylsiloxanes with thioether or ether linkages have been prepared and tested as transdermal penetration enhancers [87], The monosaccharide-modified compounds exhibited a pronounced permeation acceleration for antipyrine, while the disaccharide ether siloxane had no enhancing activity. 

Clearance tests of liver function assess a number of physiologic activities including hepatic uptake, hepatic metabolism, and hepatic excretion. Typical clearance tests of liver function include indocyanine green (ICG), antipyrine clearance test and C aminopyrine breath test. These tests give an estimation of the ability of the liver to extract and detoxify exogenous toxins (xenobiotics). Measuring the excretion of endogenously produced serum bile acids is an additional measure of hepatic clearance and has been used as a sensitive measure of early solvent hepatotoxicity." "... 

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