RESUMO
CYP1A2, CYP2D6 and N-acetyltransferase activities were estimated in 100 patients with bladder cancer and 84 control subjects from measurements of theophylline, metoprolol and isoniazid and their metabolites in urine, respectively. The frequency of occurrence of slow acetylators of isoniazid and poor metabolizers of metoprolol were 16.7% and 1.2% in the control group and 16.3% and 2.0% in the cancer patient group. These differences were not significant. The recovery ratio of 1-methyluric acid(1-MU) from theophylline was significantly higher in patients with bladder cancer than in control subjects(0.340 +/- 0.016 versus 0.260 +/- 0.020, p< 0.05). The 1-MU recovery ratio was a significant, independent risk factor among the metabolic capacities tested as shown by logistic regression analysis, controlling for N-acetylation of isoniazid, hydroxylation of metoprolol, age, sex, and smoking. We concluded that the capacity for 3-demethylation of theophylline, as a reflection of CYP1A2 activity, is significantly associated with increased risk of nonoccupational urinary bladder cancer.
Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Acetilação , Aminas/metabolismo , Neoplasias da Bexiga Urinária/enzimologia , Carcinoma de Células de Transição/enzimologia , Estudos de Casos e Controles , Citocromo P-450 CYP1A2 , Citocromo P-450 CYP2D6 , Sistema Enzimático do Citocromo P-450/metabolismo , Suscetibilidade a Doenças , Indução Enzimática , Isoniazida/farmacocinética , Coreia (Geográfico)/epidemiologia , Modelos Logísticos , Metilação , Metoprolol/farmacocinética , Pessoa de Meia-Idade , Oxigenases de Função Mista/metabolismo , Oxigenases de Função Mista/metabolismo , Oxirredutases/urina , Fumar , Teofilina/farmacocinética , Ácido Úrico/análogos & derivadosRESUMO
Constant infusion, exponentially declining infusion and program infusion of theophlline were administered to rabbits byadopting the rabbit population pharmacokinetic parameters in this laboratory, and the plasma concentrations of the drug was measured by ul- traviolet spectrophotometry. The results showed that the plasma drug concentrations following exponentially declining infusion and program infusion attained the desired steady-state level at only 30 min, though the T1/2?= 6. 08h, The median absolute value of performance error in pro-gram infusion and exponentially declining infusion was 7. 8% and 14% respectively.