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European Journal of Clinical... 1985In the present study the influence of chronic renal insufficiency on antipyrine clearance, metabolite formation and excretion was investigated in 8 patients. After oral...
In the present study the influence of chronic renal insufficiency on antipyrine clearance, metabolite formation and excretion was investigated in 8 patients. After oral administration of antipyrine, the parent compound, its metabolites and their conjugates were assayed in plasma and urine. Besides the parent drug, 3-hydroxymethylantipyrine (HMA) was present in plasma in the free and conjugated forms, whereas 4-hydroxyantipyrine (OHA) and norantipyrine (NORA) were found only in the conjugated form. The same was true for urine. The plasma concentrations of these metabolites are too low to be measured in subjects with normal renal function. Plasma antipyrine clearance in the patients was in the same range as in healthy subjects. Investigation of metabolite kinetics, however, revealed that the rate of formation of NORA was preferentially decreased, whereas that of OHA and HMA were unaltered. Renal clearance of the metabolites of antipyrine was severely impaired in patients with renal insufficiency, and the resulting accumulation made it possible for the first-time to measure the antipyrine metabolites in plasma. Mean residence times of metabolites were longer than that of the parent compound. Renal clearances of the conjugates were correlated with the creatinine clearance, but were somewhat higher. Renal clearance of free HMA was lower and was also correlated with creatinine clearance. The mean clearance for glucuronidation of HMA was 93.1 ml/min. The results suggest that in healthy subjects Phase I metabolism is the rate-limiting step in the elimination of antipyrine, which is essential for its application as a model drug in metabolism studies.
Topics: Adult; Aged; Antipyrine; Edaravone; Female; Half-Life; Humans; Kidney Failure, Chronic; Kinetics; Male; Middle Aged; Time Factors
PubMed: 4043202
DOI: 10.1007/BF00544072 -
Amyotrophic Lateral Sclerosis &... Nov 2017
Review
Topics: Amyotrophic Lateral Sclerosis; Antipyrine; Decision Making; Edaravone; Free Radical Scavengers; Humans; Treatment Outcome
PubMed: 28975816
DOI: 10.1080/21678421.2017.1369125 -
Pharmacokinetics and metabolism of antipyrine (phenazone) after intravenous and oral administration.Arzneimittel-Forschung 1982To 12 healthy male volunteers, 6 smokers and 6 non-smokers, 10 mg/kg antipyrine (phenazone) was administered i.v. and p.o. in random order. Following i.v.... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
To 12 healthy male volunteers, 6 smokers and 6 non-smokers, 10 mg/kg antipyrine (phenazone) was administered i.v. and p.o. in random order. Following i.v. administration, antipyrine kinetics could be described best by an open two-compartment model. Absolute bioavailability of an aqueous solution of antipyrine was on average 97%. Antipyrine half-life in smokers was significantly shorter (mean 9.7 h) as compared to non-smokers (mean 11.7 h). Smokers excreted significantly more 3-hydroxymethyl-antipyrine (17.2 +/- 2.4 vs. 14.2 +/- 1.9%) than non-smokers, and clearance to this metabolite was significantly increased in smokers. In addition, cumulative urinary excretion of 4-hydroxy-antipyrine, norantipyrine and 3-hydroxymethyl-antipyrine was on average higher in smokers (77.1 +/- 5.0%) as compared to non-smokers (69.5 +/- 10.8%). Thus, 3-hydroxymethyl-antipyrine formation is induced in smokers.
Topics: Administration, Oral; Adult; Antipyrine; Biological Availability; Humans; Infusions, Parenteral; Kinetics; Male
PubMed: 7201837
DOI: No ID Found -
Canadian Journal of Physiology and... Jan 1980A gas chromatographic method was developed to determine metabolites of antipyrine, norantipyhis method requires no derivatization and has ample sensitivity to determine...
A gas chromatographic method was developed to determine metabolites of antipyrine, norantipyhis method requires no derivatization and has ample sensitivity to determine these metabolites in urine after ingestion of antipyrine, a compound widely used as a hepatic probe of drug oxidation.
Topics: Adult; Antipyrine; Biotransformation; Chromatography, Gas; Dealkylation; Edaravone; Humans; Hydrolysis; Hydroxylation; Male; Middle Aged
PubMed: 7378903
DOI: 10.1139/y80-004 -
Clinical Pharmacology and Therapeutics Aug 1976A simple and senstitive radioimmunoassay has been developed for the determination of antipyrine levels in plasma and saliva of man. Antiserum to antipyrine was obtained...
A simple and senstitive radioimmunoassay has been developed for the determination of antipyrine levels in plasma and saliva of man. Antiserum to antipyrine was obtained from rabbits immunized with an immunogen prepared by covalently coupling N-(4-antipyrinyl)-succinamic acid to bovine serum albumin (BSA). The radioimmunoassay can detect antipyrine levels as low as 10 ng/ml of plasma or saliva, using a 0.1-ml sample. This contrasts with the sensitivity of a commonly used spectrophotometric method that can measure about 4,000 ng/ml using a 2-ml plasma sample. Agreement between the radioimmunoassay and spectrophotometric assay of antipyrine was excellent for plasma (r = 0.98) and salvia (r =0.97) when samples were analyzed from 6 subjects receiving 18 mg/kg of antipyrine. The correlation between plasma and saliva antipyrine half-lives using the radioimmunoassay and an 18 mg/kg dose of antipyrine was r = 0.90 (p less than 0.005). After a dose of 1.8 mg/kg of antipyrine, the drug disappeared monoexponentially from plasma and saliva for at least 51 hr, and the correlation between plasma half-life and saliva half-life was r = 0.97 (p less than 0.001) in the 6 subjects. Excellent agreement was also observed between half-lives after the high and low doses of antipyrine (r = 0.99, p less than 0.001 for plasma and r = 0.98, p less than 0.001 for saliva).
Topics: Adult; Antibody Specificity; Antipyrine; Female; Half-Life; Humans; Male; Methods; Radioimmunoassay; Saliva
PubMed: 947654
DOI: 10.1002/cpt1976202219 -
International Journal of Clinical... Feb 1995Twelve healthy subjects (6 females), who were drug-free and non alcoholic, age 21-40 years and weight 43-80 kg took part in the study which lasted about 4 weeks. The... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Twelve healthy subjects (6 females), who were drug-free and non alcoholic, age 21-40 years and weight 43-80 kg took part in the study which lasted about 4 weeks. The subjects were randomly assigned into 2 panels (of 6 subjects each) and took antipyrine (1,050 mg) orally either as powder made into solution or gelatin capsules on 3 consecutive trial occasions separated by 2-week intervals. Panel A had powder, powder and capsule formulations on trials 1, 2 and 3, respectively, and panel B had capsule, capsule and powder formulations on trials 1, 2 and 3, respectively. There were no significant differences in the saliva pharmacokinetic parameters of antipyrine in the 3 trials for both panels of subjects, except the half-lives in panel B which was significantly different at the 5% level. There were no significant differences in the amounts of antipyrine and its metabolites excreted in urine in the 3 trials. The saliva concentrations of antipyrine in the 3 trials were relatively comparable. The relative bioavailability of the capsule formulation of antipyrine was 97%. This study shows that the saliva pharmacokinetic parameters of antipyrine and the amounts of antipyrine metabolites excreted in urine are highly reproducible following repeated oral administration, either in solution or as capsules. The capsule formulation is fully bioavailable and should be suitable for oral administration in assessing the influence of drugs and environmental factors on antipyrine metabolism.
Topics: Adult; Antipyrine; Biotransformation; Capsules; Female; Half-Life; Humans; Male; Powders; Saliva
PubMed: 7757313
DOI: No ID Found -
Circulation Jun 1978The effect of propranolol on antipyrine clearance in humans was evaluated in six healthy volunteers who received single 1.4 to 1.5 g doses of intravenous antipyrine on...
The effect of propranolol on antipyrine clearance in humans was evaluated in six healthy volunteers who received single 1.4 to 1.5 g doses of intravenous antipyrine on two occasions. The first (control) antipyrine trial was without concurrent drug administration; the second trial was done during treatment with therapeutic doses of propranolol (40 mg every 4 to 6 hours). Antipyrine elimination half-life (t1/2), volume of distribution (Vd), and total clearance were determined after each trial. In all subjects isoproterenol sensitivity decreased markedly during propranolol treatment, indicating a high degree of beta blockade produced by the drug. Mean antipyrine t1/2 during the propranolol treatment period was significantly prolonged, and total clearance significantly reduced, over the control values. Twenty-four-hour urinary excretion of 4-hydroxyantipyrine, the major metabolite of antipyrine, likewise was reduced from 23.6% of the dose on the control trial to 14.8% of the dose during propranolol coadministration (0.1 less than P less than 0.2). Vd however, was nearly identical during both trials (0.62 L/kg). Thus propranolol prolongs the half-life and reduces the clearance or biotransformation rate of antipyrine, a drug whose clearance is independent of hepatic blood flow. Propranolol may influence the activity of hepatic microsomal enzymes responsible for drug hydroxylation.
Topics: Adult; Antipyrine; Female; Half-Life; Humans; Male; Propranolol
PubMed: 639239
DOI: 10.1161/01.cir.57.6.1161 -
Clinical Pharmacology and Therapeutics Jun 1985Antipyrine clearance was estimated by a one-sample technique in 14 patients with acute fever and clinical pneumonia. Antipyrine clearance during the acute illness was...
Antipyrine clearance was estimated by a one-sample technique in 14 patients with acute fever and clinical pneumonia. Antipyrine clearance during the acute illness was 31.4 +/- 7.6 ml/min (X +/- SD). Fourteen and 28 days later during convalescence, clearance values were higher (47.8 +/- 18.9 and 49.2 +/- 15.0 ml/min, respectively). We conclude that microsomal hepatic drug metabolism in adults is impaired during pneumonia.
Topics: Adult; Aged; Antipyrine; Female; Fever; Humans; Liver; Male; Metabolic Clearance Rate; Middle Aged; Pneumonia
PubMed: 4006370
DOI: 10.1038/clpt.1985.117 -
British Journal of Clinical Pharmacology May 1986The pharmacokinetics of antipyrine were examined after oral and intravenous administration to 20 epileptic subjects receiving antiepileptic drug therapy. Bioavailability...
The pharmacokinetics of antipyrine were examined after oral and intravenous administration to 20 epileptic subjects receiving antiepileptic drug therapy. Bioavailability was essentially complete (mean bioavailability 101.2% +/- 14.4 (s.d.] indicating that even in enzyme induced subjects, antipyrine behaves as a restrictively eliminated compound with negligible presystemic elimination in the gut or liver. Of the generally used measures of enzyme induction (oral clearance, oral half-life and intravenous half-life) oral clearance was the most closely related to the intravenous clearance of antipyrine (r = 0.919, P less than 0.001). Oral antipyrine administration is an alternative to intravenous administration in epileptic subjects who are enzyme-induced.
Topics: Administration, Oral; Adolescent; Adult; Antipyrine; Biological Availability; Epilepsy; Female; Half-Life; Humans; Injections, Intravenous; Kinetics; Male; Metabolic Clearance Rate; Middle Aged
PubMed: 3718808
DOI: 10.1111/j.1365-2125.1986.tb02833.x -
Life Sciences Mar 1978
Comparative Study
Topics: Antipyrine; Humans; Iodine Radioisotopes; Radioimmunoassay; Saliva
PubMed: 642701
DOI: 10.1016/0024-3205(78)90609-4