Changes in Perampanel Pharmacokinetics and Cytochrome P450 3A4 Activity Before, During, and After Pregnancy.

IF 2.8 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY
Therapeutic Drug Monitoring Pub Date : 2024-08-01 Epub Date: 2024-03-26 DOI:10.1097/FTD.0000000000001195
Yoshiaki Yamamoto, Naoto Akita, Hiroki Nogimoto, Wakana Suzuki, Katsumi Imai, Yukitoshi Takahashi, Yoshiyuki Kagawa
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Abstract

Abstract: This study evaluated perampanel pharmacokinetics and cytochrome P450 3A4 (CYP3A4) activity, assessed using the level of 4β-hydroxycholesterol (4β-OHC) as an endogenous biomarker of CYP3A4, before, during, and after pregnancy in a woman with epilepsy and compared these measurements with those from a control group of nonpregnant women with epilepsy. A 21-year-old pregnant woman was being treated with perampanel (serum concentration: 1120 ng/mL), lacosamide, and lamotrigine. After the first trimester, the lamotrigine concentration decreased markedly; however, the perampanel concentration remained almost unchanged (range, 1130-1320 ng/mL). Similarly, serum 4β-OHC levels did not change during pregnancy (before pregnancy, 78.2 ng/mL; during pregnancy, 62.2-83.2 ng/mL). To compare these measurements with those in nonpregnant women, we enrolled 27 nonpregnant women with epilepsy (age range, 16-40 years). In the control patients, we found a strong negative correlation between the concentration-to-dose ratio of perampanel and the 4β-OHC level ( r = -0.78, P < 0.001). As there was no significant change in CYP3A4 activity, we concluded that the serum perampanel concentration did not change significantly before, during, or after pregnancy. More patients need to be studied to confirm these early results.

妊娠前、妊娠期间和妊娠后培南帕奈的药代动力学和细胞色素 P450 3A4 活性的变化。
摘要:本研究评估了一名癫痫女性患者在怀孕前、怀孕期间和怀孕后的培南帕奈药代动力学和细胞色素 P450 3A4 (CYP3A4) 活性,评估采用 4β- 羟基胆固醇 (4β-OHC) 水平作为 CYP3A4 的内源性生物标记物,并将这些测量值与非怀孕癫痫女性对照组的测量值进行了比较。一名 21 岁的孕妇正在接受培南帕奈(血清浓度:1120 纳克/毫升)、拉科萨胺和拉莫三嗪的治疗。妊娠头三个月后,拉莫三嗪的浓度明显下降;然而,培南帕奈的浓度几乎保持不变(范围为 1130-1320 纳克/毫升)。同样,血清中 4β-OHC 的水平在怀孕期间也没有变化(怀孕前,78.2 纳克/毫升;怀孕期间,62.2-83.2 纳克/毫升)。为了将这些测量结果与未怀孕妇女的测量结果进行比较,我们招募了 27 名未怀孕的癫痫妇女(年龄在 16-40 岁之间)。在对照组患者中,我们发现培南帕奈的浓度剂量比与 4β-OHC 水平之间存在很强的负相关(r = -0.78,P < 0.001)。由于 CYP3A4 活性没有明显变化,我们得出结论:无论是在妊娠前、妊娠期间还是妊娠后,血清中 perampanel 的浓度都没有明显变化。我们需要对更多的患者进行研究,以确认这些早期结果。
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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来源期刊
Therapeutic Drug Monitoring
Therapeutic Drug Monitoring 医学-毒理学
CiteScore
5.00
自引率
8.00%
发文量
213
审稿时长
4-8 weeks
期刊介绍: Therapeutic Drug Monitoring is a peer-reviewed, multidisciplinary journal directed to an audience of pharmacologists, clinical chemists, laboratorians, pharmacists, drug researchers and toxicologists. It fosters the exchange of knowledge among the various disciplines–clinical pharmacology, pathology, toxicology, analytical chemistry–that share a common interest in Therapeutic Drug Monitoring. The journal presents studies detailing the various factors that affect the rate and extent drugs are absorbed, metabolized, and excreted. Regular features include review articles on specific classes of drugs, original articles, case reports, technical notes, and continuing education articles.
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