Riva R, Albani F, Ambrosetto G, Contin M, Cortelli P, Perucca E, Baruzzi A
Epilepsia. 1984 Aug;25(4):476-81. doi: 10.1111/j.1528-1157.1984.tb03446.x.
The relationship between diurnal fluctuations in free (unbound) and total plasma carbamazepine levels and the appearance of intermittent side effects was investigated in nine epileptic patients receiving chronic therapy with carbamazepine, alone or in combination with phenobarbital. On a three-times-daily or four-times-daily dosing schedule, both total and free carbamazepine levels fluctuated considerably (on an average, 41 and 45%, respectively, around the mean). Side effects (particularly diplopia and nystagmus) were observed in five patients and showed an intermittent pattern in four. Side effects were never found at total carbamazepine levels less than 34 mumol/L but invariably appeared at levels greater than 38 mumol/L. At levels between 34 and 38 mumol/L adverse effects were inconsistently observed. The correlation between plasma carbamazepine levels and manifestations of toxicity was slightly stronger when free rather than total levels were considered. Side effects were always apparent at free levels greater than 7.2 mumol/L. These data underline the limitations of relying on a single drug level determination during the monitoring of carbamazepine therapy and emphasize the necessity of carefully adjusting the dosing schedule, to minimize the appearance of intermittent adverse effects.
对9例接受卡马西平单独或联合苯巴比妥长期治疗的癫痫患者，研究了游离（未结合）血浆卡马西平水平和总血浆卡马西平水平的昼夜波动与间歇性副作用出现之间的关系。在每日三次或四次给药方案下，总卡马西平和游离卡马西平水平均有相当大的波动（平均分别在均值周围波动41%和45%）。5例患者出现副作用（尤其是复视和眼球震颤），其中4例呈间歇性模式。当总卡马西平水平低于34μmol/L时，从未发现副作用，但当水平高于38μmol/L时，副作用总是出现。在34至38μmol/L之间的水平时，不良反应的观察结果不一致。当考虑游离水平而非总水平时，血浆卡马西平水平与毒性表现之间的相关性略强。当游离水平高于7.2μmol/L时，副作用总是明显的。这些数据强调了在监测卡马西平治疗期间依赖单次药物水平测定的局限性，并强调了仔细调整给药方案以尽量减少间歇性不良反应出现的必要性。
