Perucca E, Hedges A, Makki K A, Ruprah M, Wilson J F, Richens A
Br J Clin Pharmacol. 1984 Sep;18(3):401-10. doi: 10.1111/j.1365-2125.1984.tb02482.x.
The antipyrine clearance and the urinary excretion of D-glucaric acid (D-GA) were determined in 122 patients receiving chronic anticonvulsant drug treatment and in 21 drug-free control subjects. Patients treated with carbamazepine (CBZ), phenytoin (DPH), primidone (PMD) and phenobarbitone (PB), either alone or in combination, showed higher values of antipyrine clearance and excreted larger amounts of D-GA as compared to controls. While antipyrine clearance values did not differ significantly from one drug group to another, D-GA excretion was significantly higher in patients treated with CBZ than in those treated with DPH. In patients treated with sodium valproate antipyrine clearance did not differ from control values. There was a trend for D-GA excretion to be higher in these patients but the difference was not statistically significant. Significant positive correlations were found between the dosage of CBZ, DPH, PMD and PB and both indices of enzyme induction. These data demonstrate a dose-dependent degree of enzyme induction in patients receiving therapeutic doses of these anticonvulsants. The relative potency at average dose levels for antipyrine clearance was PB (1), DPH (0.92), CBZ (0.84), PMD (0.82) and for log D-GA excretion was PB (1), CBZ (0.96), PMD (0.95), DPH (0.90).
对122例接受慢性抗惊厥药物治疗的患者及21例未服药的对照者测定了安替比林清除率及D -葡糖醛酸(D - GA)的尿排泄量。接受卡马西平(CBZ)、苯妥英(DPH)、扑米酮(PMD)和苯巴比妥(PB)单独或联合治疗的患者,与对照者相比,安替比林清除率更高,且D - GA排泄量更大。虽然各药物组之间的安替比林清除率值无显著差异,但接受CBZ治疗的患者D - GA排泄量显著高于接受DPH治疗的患者。接受丙戊酸钠治疗的患者,其安替比林清除率与对照值无差异。这些患者的D - GA排泄量有升高趋势,但差异无统计学意义。发现CBZ、DPH、PMD和PB的剂量与两种酶诱导指标之间存在显著正相关。这些数据表明,接受这些抗惊厥药物治疗剂量的患者中,酶诱导程度呈剂量依赖性。平均剂量水平下,安替比林清除率的相对效价为PB(1)、DPH(0.92)、CBZ(0.84)、PMD(0.82);log D - GA排泄的相对效价为PB(1)、CBZ(0.96)、PMD(0.95)、DPH(0.90)。