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Deutsche Medizinische Wochenschrift... Oct 1973
Topics: Adult; Aged; Anemia; Diagnosis, Differential; Female; Glomerular Filtration Rate; Humans; Hypertension; Kidney; Kidney Diseases; Leukocyte Count; Male; Middle Aged; Migraine Disorders; Phenacetin; Prognosis; Pyelonephritis; Radiography; Time Factors
PubMed: 4744371
DOI: 10.1055/s-0028-1107179 -
Veterinariia Feb 1980
Topics: Animals; Dose-Response Relationship, Drug; Drug Evaluation; Fasciola hepatica; Fascioliasis; Phenacetin; Sheep; Sheep Diseases
PubMed: 7376447
DOI: No ID Found -
Xenobiotica; the Fate of Foreign... Nov 19971. 1H-NMR spectroscopy of urine was used to determine the % deacetylation and re-acetylation of 2H-labelled (in the acetyl) phenacetin metabolites in the rat. 2. Male...
1. 1H-NMR spectroscopy of urine was used to determine the % deacetylation and re-acetylation of 2H-labelled (in the acetyl) phenacetin metabolites in the rat. 2. Male Sprague-Dawley rats were each dosed with either phenacetin or phenacetin-C2H3 at 50 mg kg-1. The total urinary recoveries for phenacetin and phenacetin-C2H3 were 47.6 +/- 16.7 and 50.1 +/- 16.2% respectively (not significantly different, p > 0.05). Paracetamol sulphate and glucuronide are the major urinary metabolites of both protio and deuteriophenacetin. 3. The futile deacetylation given by the urinary recovery of protio-acetyl metabolites of phenacetin-C2H3 was 29.6 +/- 0.9% for paracetamol sulphate and 36.6 +/- 3.1% for paracetamol glucuronide. These observations demonstrate a high level of futile deacetylation in the paracetamol conjugates formed by metabolism of phenacetin-C2H3 and this may indicate a high metabolic flux through the nephrotoxic intermediate 4-aminophenol. 4. The level of futile deacetylation for phenacetin was significantly higher than that found previously in studies of labelled paracetamol in rat or man, and may be important in understanding the higher nephrotoxicity of phenacetin as compared with paracetamol.
Topics: Acetaminophen; Acetylation; Animals; Deuterium; Magnetic Resonance Spectroscopy; Male; Phenacetin; Rats; Rats, Sprague-Dawley
PubMed: 9413921
DOI: 10.1080/004982597239930 -
Journal of Chromatography Aug 1986
Topics: Chromatography, High Pressure Liquid; Humans; Phenacetin
PubMed: 3760069
DOI: 10.1016/s0378-4347(00)83671-3 -
Drug Intelligence & Clinical Pharmacy Nov 1981
Topics: Humans; Phenacetin; Urologic Neoplasms
PubMed: 7297417
DOI: No ID Found -
Journal of Pharmaceutical Sciences Mar 2009The solubility of phenacetin, salicylic acid, and probenecid in ethanol-water and ethanol-ethyl acetate mixtures at several temperatures (15-40 degrees C) was measured....
The solubility of phenacetin, salicylic acid, and probenecid in ethanol-water and ethanol-ethyl acetate mixtures at several temperatures (15-40 degrees C) was measured. The solubility profiles are related to medium polarity changes. The apparent thermodynamic magnitudes and enthalpy-entropy relationships are related to the cosolvent action. Salicylic acid and probenecid show a single peak against the solubility parameter delta(1) of both solvent mixtures, at 40% (delta(1) = 21.70 MPa(1/2)) and 30% (delta(1) = 20.91 MPa(1/2)) ethanol in ethyl acetate, respectively. Phenacetin displays two peaks at 60% ethanol in ethyl acetate (23.30 MPa(1/2)) and 90% ethanol in water (delta(1) = 28.64 MPa(1/2)). The apparent enthalpies of solution display a maximum at 30% (phenacetin and salicylic acid) and 40% (probenecid) ethanol in water, respectively. Two different mechanisms, entropy at low ethanol ratios, and enthalpy at high ethanol ratios control the solubility enhancement in the aqueous mixture. In the nonaqueous mixture (ethanol-ethyl acetate) enthalpy is the driving force throughout the whole solvent composition for salicylic acid and phenacetin. For probenecid, the dominant mechanism shifts from entropy to enthalpy as the ethanol in ethyl acetate concentration increases. The enthalpy-entropy compensation plots corroborate the different mechanisms involved in the solubility enhancement by cosolvents.
Topics: Calorimetry, Differential Scanning; Phenacetin; Probenecid; Salicylic Acid; Solubility; Solvents; Temperature; Thermodynamics
PubMed: 18661534
DOI: 10.1002/jps.21497 -
European Journal of Clinical... 1991The metabolism of paracetamol and phenacetin has been studied in subjects previously phenotyped as either extensive or poor metabolisers of debrisoquine (EM and PM,...
The metabolism of paracetamol and phenacetin has been studied in subjects previously phenotyped as either extensive or poor metabolisers of debrisoquine (EM and PM, respectively), in order to examine the relationship between phenacetin and paracetamol activation and debrisoquine oxidation status. In separate experiments, paracetamol and phenacetin were administered orally to groups of 5 EM and 5 PM subjects, and the excretion of metabolites measured for 24 h. There were no differences between EM and PM subjects in the excretion of metabolites. After phenacetin, 0.82 of the dose was recovered in urine, mostly as paracetamol glucuronide (51%) and sulphate (30%), with smaller amounts of free paracetamol (4%) and the mercapturate (5%) and cysteine conjugates (5%), 2-hydroxyphenetidine (5%) and N-hydroxyphenacetin (0.5%). Following paracetamol, 0.87 of the dose was recovered, with similar proportions of paracetamol-derived metabolites. It is concluded that the debrisoquine oxidation phenotype is unrelated to either the metabolic activation of phenacetin and paracetamol, or to their overall metabolic clearance.
Topics: Acetaminophen; Adult; Biotransformation; Debrisoquin; Female; Humans; Male; Oxidation-Reduction; Phenacetin; Phenotype
PubMed: 1884734
DOI: 10.1007/BF00279967 -
Postgraduate Medical Journal Dec 1967
Topics: Adult; Humans; Ileostomy; Kidney Diseases; Male; Phenacetin
PubMed: 6079206
DOI: 10.1136/pgmj.43.506.791 -
Cancer Research Aug 1982Phenacetin was mutagenic in Salmonella typhimurium TA100 in plate assays when liver fractions from Aroclor-treated hamsters, but not rats, were used. Its known or...
Species-specific activation of phenacetin into bacterial mutagens by hamster liver enzymes and identification of N-hydroxyphenacetin O-glucuronide as a promutagen in the urine.
Phenacetin was mutagenic in Salmonella typhimurium TA100 in plate assays when liver fractions from Aroclor-treated hamsters, but not rats, were used. Its known or putative metabolites were synthesized; of these, N-hydroxyphenacetin and N-acetoxyphenacetin were found to be mutagenic in liquid and plate assays, both requiring activation by liver fractions from Aroclor-treated hamsters. 2-Hydroxyphenacetin and 2-acetoxyphenacetin were nonmutagenic. N-Hydroxyphenetidine (the deacetylated metabolite of phenacetin) and p-nitrosophenetole were the only products that were found to be mutagenic per se when assayed under N2 in either Salmonella TA100 and TA100 NR (nitroreductase-deficient) strains. Phenacetin was administered to male BDVI rats and Syrian golden hamsters, and its urinary metabolites were deconjugated with beta-glucuronidase:arylsulfatase. After reactivation by hamsters liver fractions, mutagenicity was demonstrated in S. typhimurium TA100 with urine from phenacetin-treated hamsters, but not with that from rats. After treatment with deconjugating enzymes, N-hydroxyphenacetin was isolated from hamster urine by high-performance liquid chromatography and identified by mass spectral analysis. The data support the conclusions that (a) N-hydroxyphenacetin is a proximate mutagenic metabolite of phenacetin which, after N-deacylation, is responsible for the mutagenicity observed in vitro and in the urine of hamsters and (b) the higher yield of N-hydroxyphenacetin that is formed in the liver of hamsters as compared to rats explains the pronounced species-specific activation of phenacetin into bacterial mutagens.
Topics: Animals; Biotransformation; Kinetics; Liver; Male; Mutagenicity Tests; Mutagens; Mutation; Phenacetin; Rats; Rats, Inbred Strains; Salmonella typhimurium
PubMed: 7046920
DOI: No ID Found -
Clinical Pharmacology and Therapeutics 1969
Topics: Aged; Chromatography, Thin Layer; Female; Humans; Kidney Diseases; Male; Middle Aged; Phenacetin
PubMed: 5795807
DOI: 10.1002/cpt1969103383