群体药动学原理建立卡马西平和丙戊酸的定时定量给药模型及临床应用

发布时间：2018-03-04 14:32

本文选题：定时定量给药　切入点：卡马西平　出处：《中国医院药学杂志》2015年12期 　论文类型：期刊论文

【摘要】：目的:建立国人卡马西平和丙戊酸的群体药动学模型,并将其应用于临床,建立定时定量给药的癫痫临床药学服务模式。方法:筛选国内多中心卡马西平(carbamazepine,CBZ)和丙戊酸(valproic acid,VPA)的稳态谷浓度数据,建立适合神经内科癫痫患者个体化给药的群体药动学(population pharmacokinetics,PPK)模型,利用建模中心外数据评价所建模型的预测能力。结果:建立了CBZ的PPK最终模型:Ka(h-1)=1.2,CL(CL/F)(L·h-1)=0.074×TAMTCBZ0.41×WT0.267×1.42(若合用苯妥因钠,否则为1)×1.18(若合用苯巴比妥,否则为1)×0.84(若年龄65岁,否则为1),V(V/F)(L)=1.21×WT;VPA的PPK最终模型:Ka(h-1)=1.9,CL(CL/F)(L·h-1)=0.102×(WT/60)0.696×TAMTVPA0.197×1.36(若合用CBZ,否则为1)×1.25(若合用苯妥英钠,否则为1)×1.11(若合用苯巴比妥,否则为1),V(V/F)(L)=0.14×WT;其中,Ka为吸收速率常数,CL为表观清除率,V为表观分布容积,F为生物利用度,TAMTCBZ、TAMTVPA为CBZ、VPA的日剂量(mg·d-1),WT为体质量(kg)。经建模中心外数据验证,所建模型预测能力较强。建立的定时定量药学服务应用于临床后,取得了较好的临床疗效(案例略)。结论:新临床药学服务有助于医疗团队提高抗癫痫治疗质量。
[Abstract]:Objective: to establish a population pharmacokinetic model of carbamazepine and valproic acid in Chinese and to apply them to clinical practice. Methods: the steady-state valley concentration data of carbamazepine (CBZ) and valproic acid (VPA) of carbamazepine (carbamazepine) and valproic acid (VPA) were selected. A population pharmacokinetic population pharmacokinetic PKK model was established for patients with epilepsy in neurology department, and the predictive ability of the model was evaluated by using the data outside the modeling center. Results: the final PPK model of CBZ was established. The final model of PPK was established. The PPK model of CBZ was 0.074 脳 TAMTCBZ0.41 脳 WT0.267 脳 1.42 (combined with benzoin sodium). Otherwise, it is 1) 脳 1.18 (if phenobarbital is used, otherwise it is 1) 脳 0.84 (if age 65 years old, otherwise, 1.21 脳 WTA VPA), the final PPK model of PPK is: Kah-1n 1.9C L 路h-1 0.102 脳 WTP 6096 脳 TAMTVPA0.197 脳 1.36 (if combined with CBZ, otherwise, 1) 脳 1.25 (if phenytoin sodium is used, otherwise it is 1) 脳 1.11 (if phenobarbital is used, otherwise, it is 1) 脳 1.11 (if phenobarbital is used, it is 0.102 脳 WTP 6096 脳 TAMTVPA0.197 脳 1.36) 脳 1.11 (if phenobarbital is used, otherwise it is 1). Otherwise, it is 0.14 脳 WT0.14 脳 WT.where Ka-Ka is the absorption rate constant, CL is the apparent clearance rate and V is the apparent distribution volume, F is the bioavailability and the daily dose of TAMTCBZ / TAMTVPA is CBZ / VPA, the daily dose of TAMTCBZ / TAMTVPA is CBZN / VPA, and the body weight is kg / kg. The established model has strong predictive ability. The established timing and quantitative pharmaceutical care has achieved good clinical effect after its application in clinical practice. Conclusion: the new clinical pharmacological care is helpful to improve the quality of antiepileptic treatment in the medical team.
【作者单位】：福建医科大学附属第一医院药学部;福建医科大学附属第一医院神经内科;复旦大学附属华山医院药剂科;
【基金】：福建医学创新基金课题(编号:2012-CX-22) 福建省自然科学基金课题(编号:2013J01370)
【分类号】：R969.1

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