Lloyd P, Flesch G, Dieterle W
Department of Clinical Pharmacology, Ciba Pharmaceuticals, Horsham, England.
Epilepsia. 1994;35 Suppl 3:S10-3. doi: 10.1111/j.1528-1157.1994.tb05938.x.
Oxcarbazepine (OCBZ) is a new antiepileptic drug (AED) structurally related to carbamazepine (CBZ) but differing in several important aspects, notably metabolism and induction of metabolic pathways. Consequently, OXCB has fewer drug-drug interactions compared with CBZ. Absorption of OCBZ is rapid and complete. In animals it is responsible for the pharmacological effect. In humans, however, the parent compound is rapidly and extensively metabolized to a monohydroxy derivative (MHD), which is responsible for the therapeutic effect. Exposure to the MHD increases dose proportionally, and steady state is achieved after only three or four doses in a twice-daily regimen. When given with food, systemic exposure to MHD increases by about 17%. MHD is eliminated with a half-life of about 8-10 h. About 27% of the dose is recovered in the urine as unchanged MHD and a further 49% as a glucuronide conjugate of MHD. Results suggest that the kinetics of OCBZ should not be affected by impaired liver function. Impaired kidney function does not affect the kinetics of MHD; the glucuronide conjugate will, however, accumulate in these patients. The conversion of OCBZ to MHD is catalyzed by reductase enzymes, which are not subject to induction. Furthermore, OCBZ itself does not appear to induce the cytochrome P-450 family in general, although it does induce the P-450 IIIA subfamily, which is responsible for the metabolism of estrogens and the dihydropyridine calcium-channel blockers (e.g., nifedipine, felodipine). In patients, linear and dose-proportional kinetics with no autoinduction of metabolism simplify OCBZ dosage adjustment.
奥卡西平（OCBZ）是一种新型抗癫痫药物（AED），在结构上与卡马西平（CBZ）相关，但在几个重要方面有所不同，尤其是代谢和代谢途径的诱导。因此，与CBZ相比，奥卡西平的药物相互作用较少。奥卡西平的吸收迅速且完全。在动物中，它具有药理作用。然而，在人类中，母体化合物会迅速且广泛地代谢为单羟基衍生物（MHD），后者具有治疗作用。MHD的暴露量随剂量成比例增加，在每日两次给药方案中，仅需三或四次给药即可达到稳态。与食物一起服用时，MHD的全身暴露量会增加约17%。MHD的消除半衰期约为8 - 10小时。约27%的剂量以未改变的MHD形式在尿液中回收，另有49%以MHD的葡萄糖醛酸共轭物形式回收。结果表明，肝功能受损不应影响奥卡西平的动力学。肾功能受损不影响MHD的动力学；然而，葡萄糖醛酸共轭物会在这些患者体内蓄积。奥卡西平向MHD的转化由还原酶催化，这些酶不会被诱导。此外，奥卡西平本身一般似乎不会诱导细胞色素P - 450家族，尽管它确实会诱导负责雌激素和二氢吡啶类钙通道阻滞剂（如硝苯地平、非洛地平）代谢的P - 450 IIIA亚家族。在患者中，线性和剂量成比例的动力学以及无代谢自身诱导现象简化了奥卡西平的剂量调整。
