Population toxicokinetics of carbamazepine and its metabolite carbamazepine-10,11-epoxide in adults.

Vladan Lukic, Slobodan M Jankovic, Nemanja Z Petrovic, Slavica Vucinic, Jasmina Jovic Stosic, Snezana Djordjevic, Viktorija Dragojevic-Simić
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Abstract

Background: Carbamazepine is one of the most commonly used antiseizure medications. Although carbamazepine pharmacokinetics in epileptic patients is well described, much less is known about these processes in the patients who experienced self-poisoning episode by this drug. Therefore, the aim of our investigation was to perform population toxicokinetics of carbamazepine and its metabolite carbamazepine-10,11-epoxide in adults.

Research design and methods: Software program NONMEM and the ADVAN2 TRANS2 subroutine were used for establishing a population toxicokinetic model for the estimation of clearance and volume of distribution based on of the sum values of carbamazepine and carbamazepine-10,11-epoxide concentrations.

Results: Our results indicated that the adult patients' ability to eliminate carbamazepine and carbamazepine-10,11-epoxide following acute carbamazepine self-poisoning was strongly associated with the high levels of CRP and ASP, as well as by the treatment with sedation.

Conclusions: Our study should provide better understanding of the toxicokinetics of carbamazepine taken in overdose and better management of patient population admitted to hospital.

成人体内卡马西平及其代谢物卡马西平-10,11-环氧化物的人群毒物动力学。
背景:卡马西平是最常用的抗癫痫药物之一:卡马西平是最常用的抗癫痫药物之一。虽然卡马西平在癫痫患者体内的药代动力学已被充分描述,但对使用该药物发生自我中毒的患者体内的这些过程却知之甚少。因此,我们调查的目的是研究卡马西平及其代谢物卡马西平-10,11-环氧化物在成人中的群体毒代动力学:采用NONMEM软件和ADVAN2 TRANS2子程序建立群体毒物动力学模型,根据卡马西平和卡马西平-10,11-环氧化物浓度的总和值估算清除率和分布容积:我们的研究结果表明,急性卡马西平自中毒后,成年患者清除卡马西平和卡马西平-10,11-环氧化物的能力与高水平的CRP和ASP以及镇静治疗密切相关:我们的研究有助于更好地了解过量服用卡马西平的毒代动力学,从而更好地管理入院患者。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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