Chen Zhuo-Jia, Wang Xue-Ding, Zhou Lie-Min, Fang Zi-Yan, Wang Hong-Sheng, Li Jia-Li, Zhou Jue-Qian, Huang Hong-Bing, Huang Min
Yao Xue Xue Bao. 2014 Apr;49(4):530-4.
To investigate the effects of carbamazepine (CBZ) on the plasma concentrations of valproic acid (VPA) and its toxic metabolite 2-propyl-4-pentenoic acid (4-ene VPA) in epileptic patients, the plasma concentrations of VPA and 4-ene VPA were determined, and the effect of CBZ on pharmacokinetics of VPA was evaluated. All patients had been divided into two groups (VPA group, n = 87; and VPA+CBZ group, n = 19). As compared to VPA group, the combination of CBZ significantly (P < 0.01) decreased the trough concentration of VPA [VPA group, (69.5 +/- 28.8) microg x mL(-1); VPA+CBZ group, (46.3 +/- 25.6) microg x mL(-1)] and does-adjusted VPA trough concentration [VPA group, (4.89 +/- 2.21) microg x mL(-1) x mg(-1) x kg(-1); VPA+CBZ group, (3.14 +/- 1.74) microg x mL(-1) x mg(-1) x kg(-1)]. However, the addition of CBZ did not influence the concentration of 4-ene VPA. The present study revealed that coadministration of CBZ can reduce VPA plasma concentration and may impact VPA clinical effect, therefore therapeutic drug mornitoring of VPA should be used when combined use of CBZ and VPA.
为研究卡马西平（CBZ）对癫痫患者丙戊酸（VPA）及其毒性代谢产物2-丙基-4-戊烯酸（4-烯VPA）血药浓度的影响，测定了VPA和4-烯VPA的血药浓度，并评估了CBZ对VPA药代动力学的影响。所有患者被分为两组（VPA组，n = 87；VPA + CBZ组，n = 19）。与VPA组相比，联合使用CBZ显著（P < 0.01）降低了VPA的谷浓度[VPA组，（69.5 ± 28.8）μg·mL⁻¹；VPA + CBZ组，（46.3 ± 25.6）μg·mL⁻¹]以及剂量校正后的VPA谷浓度[VPA组，（4.89 ± 2.21）μg·mL⁻¹·mg⁻¹·kg⁻¹；VPA + CBZ组，（3.14 ± 1.74）μg·mL⁻¹·mg⁻¹·kg⁻¹]。然而，添加CBZ并未影响4-烯VPA的浓度。本研究表明，联合使用CBZ可降低VPA的血药浓度，并可能影响VPA的临床疗效，因此在联合使用CBZ和VPA时应进行VPA的治疗药物监测。
