Valproic acid pharmacokinetics in children. IV. Effects of age and antiepileptic drugs on protein binding and intrinsic clearance
Valproic acid pharmacokinetics in children. IV. Effects of age and antiepileptic drugs on protein binding and intrinsic clearance
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丙戊酸在儿童中的药代动力学。
DOI：
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发表时间：
1993
期刊：
影响因子：
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通讯作者：
D. M. Kraus
中科院分区：
文献类型：
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作者：
J. Cloyd;J. Fischer;R. Kriel;D. M. Kraus
采用多元逐步线性回归分析48例服用丙戊酸患儿的药代动力学数据。接受酶诱导抗癫痫药物治疗的儿童（n = 27）与接受单一治疗的儿童相比，清除率、消除率和剂量要求更高（p < 0.01），药代动力学值的变异性更大（p < 0.05）。年龄和多种治疗解释了患者间总清除率（r2 = 0.80; p < 0.001）和内在清除率（r2 = 0.77; p < 0.001）和清除率（r2 = 0.61; p < 0.002）的大部分差异。游离分数变异与丙戊酸盐浓度和苯巴比妥相关（r2 = 0.47; p < 0.001）。分布体积方差与游离分数相关（r2 = 0.48; p < 0.001）。年龄和多种治疗对丙戊酸清除率的影响主要归因于代谢的变化，而不是蛋白质结合的变化。对于接受其他酶诱导抗癫痫药物的儿童，丙戊酸的剂量要求更大，变化更大。
Pharmacokinetic data from 48 children who were taking valproic acid were analyzed by multiple step‐wise linear regression. Children who were receiving enzyme‐inducing antiepileptic drugs (n = 27) had greater (p < 0.01) clearances, elimination rates, and dosage requirements and greater (p < 0.05) variability in pharmacokinetic values than patients receiving monotherapy. Age and polytherapy explained most of the interpatient variability in total (r2 = 0.80; p < 0.001) and intrinsic (r2 = 0.77; p < 0.001) clearances and the elimination rate (r2 = 0.61; p < 0.002). Free fraction variability was related to valproate concentration and phenobarbital (r2 = 0.47; p < 0.001). Distribution volume variance was associated with free fraction (r2 = 0.48; p < 0.001). The effect of age and polytherapy on valproate clearance is primarily attributable to changes in metabolism rather than in protein binding. Valproic acid dosage requirements are greater and more variable for children who are receiving other enzyme‐inducing antiepileptic drugs.