ABSTRACT
Acute treatment of rabbits with pargyline (50 mg/kg, ip, 30 min before tolbutamide) significantly increased the elimination half life and AUC0-->infinity of tolbutamide resulting in prolonged hypoglycaemia. Similar treatment also prolonged the half life of antipyrine which is used as model drug to indicate hepatic microsomal enzyme activity in vivo confirming that pargyline treatment delayed the elimination of tolbutamide in rabbits by inhibiting its hepatic metabolism.
Subject(s)
Animals , Antipyrine/pharmacokinetics , Blood Glucose/analysis , Drug Interactions , Female , Half-Life , Hypoglycemia/chemically induced , Injections, Intraperitoneal , Male , Microsomes, Liver/drug effects , Pargyline/administration & dosage , Rabbits , Tolbutamide/administration & dosageABSTRACT
A atividade de formas especificas do citocromo P450 foi caracterizada "in vivo", em pacientes portadores de insuficiencia renal cronica moderada, atraves da administracao dos farmacos marcadores antipirina e nifedipina na forma de "coquetel". Foram investigados nove pacientes portadores de hipertensao arterial e insuficiencia renal cronica moderada e dez pacientes portadores de hipertensao arterial com funcao renal normal. Atraves do "clearance" total da nifedipina e do "clearance" de formacao de cada produto de biotransformacao da antipirina, 3-hidroximetilantipirina (HMA), norantipirina (NORA) e 4-hidroxiantipirina (OHA) foram caracterizadas quatro formas distintas do citocromo P450. Mostraram-se induzidas nos pacientes portadores de insuficiencia renal cronica moderada as formas de citocromo P450 associadas com a formacao da NORA e da desidronifedipina (citocromo P450 III A4). O estudo evidencia seletividade nas formas induzidas justificando o aumento da velocidade de biotransformacao oxidativa de alguns medicamentos na insuficiencia renal cronica
Subject(s)
Humans , Male , Female , Adult , Antipyrine/pharmacokinetics , Antipyrine/therapeutic use , Cytochrome P-450 Enzyme System/metabolism , Hypertension/drug therapy , Renal Insufficiency, Chronic/drug therapy , Nifedipine/pharmacokinetics , Nifedipine/therapeutic use , Administration, Oral , BiotransformationABSTRACT
Avaliaram-se as alteracoes na eliminacao da antipirina e de seus principais produtos de biotransformacao , 3-hidroximetilantipirina (3HMA), 4-hidroxiantipirina (4HOA) e norantipirina (NORA) em pacientes portadores de doencas hepaticas. Investigaram-se onze pacientes com cirrose hepatica confirmada por biopsia, nove pacientes com esquistossomose hepatesplenica e vinte e cinco voluntarios sadios. Os "clearances" total e hepatico da antipirina foram reduziods com prolongamento de sua meia-vida de eliminacao nos pacientes cirroticos. Os "clearances" de formacao da 3HMA, 4HOA e NORA tambem foram reduzidos como consequencia de seu comprometimento hepatico. Os pacientes com esquistossomose hepatesplenica mostraram alteracoes no metabolismo da antipirina, afetando os "clearances" de formacao da 3HMA e da 4HOA, enquanto que para a NORA este parametro manteve-se inalterado. Deste modo, a determinacao do "clearance" total da antipirina e da excrecao urinaria da antipirina e seus principais produtos de biotransformacao mostrou ser teste util para avaliar o metabolismo oxidativo nas doencas hepaticas
Subject(s)
Humans , Antipyrine/pharmacokinetics , Biotransformation , Liver Diseases/metabolism , Antipyrine/blood , Antipyrine/therapeutic use , Antipyrine/urine , Liver Cirrhosis/drug therapy , Liver Diseases/drug therapy , Schistosomiasis/drug therapyABSTRACT
Pathological conditions are known to affect pharmacokinetics of many drugs. Antipyrine half-life is used as a marker of liver microsomal enzyme function. Antipyrine pharmacokinetics, therefore, was investigated in 23 thyrotoxic and 11 euthyroid goitre patients. Of these, 11 thyrotoxic and 9 euthyroid goitre patients also participated in doxycycline bioavailability studies. In thyrotoxic patients, antipyrine half-life and AUCo infinity and doxycycline Cpmax and AUCo infinity were found to be reduced as compared to those of healthy euthyroid normal subjects. Following treatment of thyrotoxicosis, the antipyrine half-life and AUCo infinity returned to normal. Doxycycline AUCo infinity returned to near normal range but Cpmax did not.
Subject(s)
Administration, Oral , Adult , Antipyrine/pharmacokinetics , Biological Availability , Doxycycline/pharmacokinetics , Female , Goiter/metabolism , Half-Life , Humans , Male , Middle Aged , Thyrotoxicosis/metabolismABSTRACT
A prospective study was undertaken to determine prognostic markers for patients with obstructive jaundice. Along with routine liver function tests, antipyrine clearance was determined in 20 patients. Four patients died after basal investigations. Five patients underwent definitive surgery. The remaining 11 patients were subjected to percutaneous transhepatic biliary decompression. Four patients died during the drainage period, while surgery was carried out for seven patients within 1-3 weeks of drainage. Of 20 patients, only six patients survived. Basal liver function tests were comparable in survivors and nonsurvivors. Discriminant analysis of the basal data revealed that plasma bilirubin, proteins and antipyrine half-life taken together had a strong association with mortality. A mathematical equation was derived using these variables and a score was computed for each patient. It was observed that a score value greater than or equal to 0.84 indicated survival. Omission of antipyrine half-life from the data, however, resulted in prediction of false security in 55% of patients. This study highlights the importance of addition of antipyrine elimination test to the routine liver function tests for precise identification of high risk patients.