ABSTRACT
The ability of feprazone to induce the hepatic microsomal mixed-function oxidases was investigated in the rat, with emphasis being placed on the nature of the cytochrome P-450 family induced. Treatment with feprazone enhanced the p-hydroxylation of aniline and the dealkylations of benzphetamine and pentoxyresorufin but had no effect on the O-deethylation of ethoxyresorufin. The same treatment had no major effect on total cytochrome P-450 levels but increased the spectral interaction of metyrapone with reduced cytochrome P-450. Immunoblots employing monospecific polyclonal antibodies revealed that feprazone induces the apoprotein levels of the P450 II B, but not of the P450 I, family. It is concluded that feprazone is an inducer of the rat hepatic mixed-function oxidase system showing selectivity toward the P450 II B family.
Subject(s)
Cytochrome P-450 Enzyme System/biosynthesis , Feprazone/pharmacology , Phenylbutazone/analogs & derivatives , Animals , Antibodies , Body Weight/drug effects , Computer Simulation , Cytosol/enzymology , Enzyme Induction , Glutathione Transferase/metabolism , Immunoblotting , Liver/anatomy & histology , Liver/enzymology , Liver/ultrastructure , Male , Mixed Function Oxygenases/biosynthesis , Molecular Structure , NADP/metabolism , Organ Size/drug effects , Rats , Rats, Inbred StrainsABSTRACT
Os autores trataram 35 pacientes em intervençoes odontológicas diversas. Estes casos foram divididos em três grupos, de acordo com as entidades clínicas tratadas. O grupo I incluiu 12 pacientes, nos quais foram realizados tratamentos endodônticos, sendo que em 2, simultaneamente, foram realizadas cirurgias (curetagem de bolsas periodontais e extraçoes múltiplas). O grupo II incluiu 9 pacientes, que foram submetidos a cirurgias bucais menores, tais como extraçoes múltiplas, epicetomias e devido a problemas periodontais. O grupo III era constituído por 12 pacientes de ambos os sexos, submetidos a cirurgias mais extensas. Sua idade variou entre 7 e 60 anos. A todos os pacientes foi administrada a feprazona, na dose de 1 cápsula de 12 em 12 horas, durante quatro dias. Efeitos colaterais surgiram em dois casos; foi necessário suspender o medicamento em apenas um paciente, que apresentou erupçao cutânea
Subject(s)
Child , Adolescent , Adult , Middle Aged , Humans , Male , Female , Anti-Inflammatory Agents , Dentistry, Operative , Feprazone/pharmacology , Feprazone/therapeutic useABSTRACT
The inducing effect of feprazone, a pyrazolone anti-inflammatory agent, on hepatic drug-metabolizing enzymes has been studied in healthy volunteers. The ratio of 6 beta-hydroxycortisol (6 beta-OHF) to 17-hydroxycorticosteroids (17-OHCS) in urine, used as an indicator of oxidative drug-metabolizing enzyme activity, was increased up to 1.6-times the original level after 5 days of oral treatment with feprazone 300 mg/day. This indicates that feprazone induces hepatic drug-metabolising enzymes in man as does phenylbutazone.
Subject(s)
Feprazone/pharmacology , Liver/enzymology , Mixed Function Oxygenases/biosynthesis , Phenylbutazone/analogs & derivatives , 17-Hydroxycorticosteroids/metabolism , Adult , Enzyme Induction/drug effects , Female , Humans , Hydrocortisone/analogs & derivatives , Hydrocortisone/metabolism , Liver/drug effects , MaleABSTRACT
Some drugs, including nonsteroidal antiinflammatory compounds, can be hemolytic in glucose-6-phosphate dehydrogenase-deficient patients. We have studied the potential hemolytic activity of feprazone, a nonsteroidal antiinflammatory compound in vitro and in vivo. Agents that may be hemolytic for glucose-6-phosphate dehydrogenase-deficient erythrocytes will stimulate the hexose monophosphate shunt in normal erythrocytes. Eleven normal subjects were treated with feprazone and their erythrocytes were incubated in their own sera (containing active feprazone metabolites) and [1-14C]-glucose. Because no statistically significant increase in 14CO2 evolution was observed, 15 pediatric male patients with glucose-6-phosphate dehydrogenase deficiency who required antiinflammatory treatment were treated with feprazone. No hemolytic crises and no statistically significant changes of hematologic tests were observed.
Subject(s)
Feprazone/pharmacology , Glucosephosphate Dehydrogenase Deficiency/blood , Hemolysis/drug effects , Phenylbutazone/analogs & derivatives , Adolescent , Adult , Erythrocytes/drug effects , Feprazone/adverse effects , Humans , MaleSubject(s)
Anti-Inflammatory Agents/therapeutic use , Feprazone/analogs & derivatives , Phenylbutazone/analogs & derivatives , Animals , Arthritis/drug therapy , Arthritis, Experimental/drug therapy , Dogs , Feprazone/pharmacology , Feprazone/therapeutic use , Gastric Mucosa/drug effects , Granuloma/drug therapy , Guinea Pigs , Mice , Pleurisy/drug therapy , RatsSubject(s)
Anti-Inflammatory Agents/pharmacology , Anticoagulants/pharmacology , Feprazone/pharmacology , Phenylbutazone/analogs & derivatives , Phenylbutazone/pharmacology , Pyrazoles/pharmacology , Warfarin/pharmacology , Adult , Clinical Trials as Topic , Drug Interactions , Female , Humans , Male , Middle Aged , Prothrombin Time , Time FactorsABSTRACT
Two studies are reported; a double-blind cross-over trial of feprazone 600 mg daily and aspirin 3.6 g daily in the treatment of rheumatoid arthritis, and an uncontrolled open study of gastrointestinal tolerance in twenty rheumatoid arthritis patients with known intolerance to other drugs. The first study showed that feprazone was significantly superior to aspirin in all the parameters tested. In the second study all twenty patients showed an improvement of their gastrointestinal symptoms, nineteen reporting no symptoms at all when taking the new preparation.
