Influence of Inflammation on the Pharmacokinetics of Perampanel.
Influence of Inflammation on the Pharmacokinetics of Perampanel.
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炎症对吡仑帕奈药代动力学的影响。
DOI：
10.1097/ftd.0000000000000556
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发表时间：
2018
影响因子：
2.5
通讯作者：
Inoue Y
中科院分区：
文献类型：
--
作者：
Yamamoto Y;Takahashi Y;Horino A;Usui N;Nishida T;Imai K;Kagawa Y;Inoue Y
背景：众所周知，炎症对各种药物的药代动力学有影响。本研究探讨C-反应蛋白(CRP；一种炎症标志物)与潘生丁药代动力学的关系。方法：在111例同时接受CRP和潘生丁测定的患者中，有23例患者的血清CRP水平超过1.5 mg/dL(CRP阳性)。我们比较了这23例患者在C反应蛋白阳性和阴性时的药物浓度/剂量比(CD比)。结果：在10例使用酶诱导抗癫痫药物(AEDs)的患者中，当CRP阳性时，CD比率从1389增加到2132(ng/mL)/(mg/kg)，平均CD比率增加53.5%。13例无酶诱导性AEDs的患者，C反应蛋白阳性时，CD比值平均升高100.8%[由3826 ng/mL增至7683 ng/mL/(mg/kg)]。多元回归分析显示，C反应蛋白水平是影响外周CD比率的显著独立决定因素。尽管CD比率显著增加，但没有不良事件的报道。结论：无论同时使用酶诱导的AEDs，炎症患者的血清PAMPANET浓度均显著增加。然而，这种增加与中枢神经系统毒性无关。虽然目前尚不清楚是否增加了游离和/或结合的膜面板浓度，但似乎没有必要降低剂量以提高炎症患者的血清膜面板水平。
Background:It is well-known that the pharmacokinetics of various drugs are influenced by inflammation. This study evaluated the relationship between C-reactive protein (CRP; an inflammation marker) and the pharmacokinetics of perampanel.Methods:Among 111 patients who underwent measurement of both CRP and perampanel, 23 patients had a serum CRP level exceeding 1.5 mg/dL (CRP-positive). We compared the concentration/dose ratio (CD ratio) of perampanel in these 23 patients between the times when they were CRP-positive and CRP-negative. To evaluate the effect of CRP on the CD ratio, multiple regression analysis was performed with the following covariates: CRP-positive status, body weight, and use of phenytoin, carbamazepine, or phenobarbital, and combinations of these drugs.Results:In 10 patients using enzyme-inducing antiepileptic drugs (AEDs), the mean CD ratio increased by 53.5%[from 1389 to 2132 (ng/mL)/(mg/kg)] when they were CRP-positive. In 13 patients without enzyme-inducing AEDs, the mean CD ratio increased by 100.8%[from 3826 ng/mL to 7683 (ng/mL)/(mg/kg)] when they were CRP-positive. By multiple regression analysis, the CRP level was a significant independent determinant of the CD ratio of perampanel. Despite a marked increase of the CD ratio, no adverse events were reported.Conclusions:Irrespective of concomitant administration of enzyme-inducing AEDs, the serum perampanel concentration showed a marked increase in patients with inflammation. However, this increase was not associated with central nervous system toxicity. Although it is unknown whether the concentration of free and/or bound perampanel was increased, it seems likely that dose reduction is unnecessary for elevation of the serum perampanel level in patients with inflammation.