Hartley R, Lucock M D, Ng P C, Forsythe W I, McLain B, Bowmer C J
Department of Paediatrics and Child Health, England.
Ther Drug Monit. 1990 Sep;12(5):438-44. doi: 10.1097/00007691-199009000-00006.
The relationship between daily dose and plasma concentrations of carbamazepine (CBZ), CBZ-10,11-epoxide (CBZ-EP), and 10,11-dihydro-10,11-trans-dihydroxy-CBZ (CBZ-DIOL) was investigated in 21 children aged 7-16 years who received CBZ monotherapy, twice daily in equally divided doses. Significant linear correlations between CBZ dose and plasma levels were obtained for CBZ and its metabolites (p less than 0.01). In addition, the effects of daily dose and patients' age on the plasma level/dose ratios for CBZ, CBZ-EP, and CBZ-DIOL were evaluated. A significant negative correlation was observed between the daily dose of CBZ and the CBZ plasma level/dose ratio (p less than 0.01). By contrast, plasma level/dose ratios for CBZ-EP and CBZ-DIOL were independent of dose (p greater than 0.1). On the basis of these observations, we consider that the decrease in CBZ plasma level/dose ratio with increasing CBZ dose appears to be due to dose-dependent metabolic clearance of CBZ. The influence of age on plasma level/dose ratios for CBZ and its metabolites was not significant (p greater than 0.05). However, there was considerable interdose and diurnal variation in the plasma level/dose ratios, particularly for CBZ (28-41%); this must be taken into account when making dose adjustments based on plasma level/dose ratios.
在21名7至16岁接受卡马西平（CBZ）单一疗法的儿童中，研究了每日剂量与卡马西平（CBZ）、卡马西平-10,11-环氧化物（CBZ-EP）和10,11-二氢-10,11-反式-二羟基-CBZ（CBZ-DIOL）血浆浓度之间的关系，这些儿童每日分两次等量服用CBZ。CBZ及其代谢产物的CBZ剂量与血浆水平之间存在显著的线性相关性（p小于0.01）。此外，还评估了每日剂量和患者年龄对CBZ、CBZ-EP和CBZ-DIOL血浆水平/剂量比值的影响。观察到CBZ的每日剂量与CBZ血浆水平/剂量比值之间存在显著的负相关（p小于0.01）。相比之下，CBZ-EP和CBZ-DIOL的血浆水平/剂量比值与剂量无关（p大于0.1）。基于这些观察结果，我们认为随着CBZ剂量增加，CBZ血浆水平/剂量比值降低似乎是由于CBZ的剂量依赖性代谢清除。年龄对CBZ及其代谢产物血浆水平/剂量比值的影响不显著（p大于0.05）。然而，血浆水平/剂量比值存在相当大的剂量间期和昼夜变化，尤其是CBZ（28%-41%）；在根据血浆水平/剂量比值进行剂量调整时，必须考虑到这一点。
