与乙型肝炎病毒衣壳组装调节剂 JNJ-56136379 (Bersacapavir) 的药物

StephenW

与乙型肝炎病毒衣壳组装调节剂 JNJ-56136379 (Bersacapavir) 的药物相互作用
Joris Vandenbossche 1 , Jeysen Yogaratnam 2 , Vera Hillewaert 1 , Freya Rasschaert 1 , Willem Talloen 1 , Jeike Biewenga 1 , Jan Snoeys 1 , Thomas N Kakuda 2 , Martyn Palmer 3 , Julius Nangosyah 1 , Michael Biermer 1
隶属关系
隶属关系

    1
    Janssen Pharmaceutica NV，Beerse，比利时。
    2
    Janssen Research & Development，南旧金山，加利福尼亚，美国。
    3
    Janssen Research & Development，美国宾夕法尼亚州 Spring House。

    PMID：36062869 DOI：10.1002/cpdd.1164

抽象的

衣壳组装调节剂 JNJ-56136379 (bersacapavir) 可破坏乙型肝炎病毒的复制。它通过细胞色素 P450 (CYP) 3A 代谢，但对于 JNJ-56136379 与抑制 CYP3A 或被 CYP3A 代谢的药物联合使用时的药物相互作用知之甚少。在一项 1 期开放标签试验 (NCT03945539) 中，健康成人接受了 1 剂 JNJ-56136379，之前暴露于 200 mg 伊曲康唑（CYP3A 抑制剂）的 21 天有无。在第二阶段 1 开放标签试验 (NCT03111511) 中，健康女性在 JNJ-56136379 15 天之前和之后接受 1 剂屈螺酮/乙炔雌二醇和咪达唑仑。伊曲康唑使 JNJ-56136379 的血浆浓度-时间曲线下面积 (AUC) 增加了 38%。 JNJ-56136379 将咪达唑仑（CYP3A 底物）的最大观察浓度和 AUC 降低了 42%-54%，乙炔雌二醇的 AUC 增加了 1.6 倍，但对屈螺酮的药代动力学没有影响。总体而言，这些结果表明强效 CYP3A 抑制剂（伊曲康唑）适度增加了 JNJ-56136379 的暴露量。此外，JNJ-56136379 是 CYP3A（咪达唑仑）的弱诱导剂，并增加了乙炔雌二醇的暴露量；不建议同时服用高剂量雌激素类避孕药和 JNJ-56136379。

关键词：CYP3A； JNJ-56136379；衣壳组装调节剂；药物-药物相互作用；乙型肝炎。

© 2022 作者。药物开发中的临床药理学由 Wiley Periodicals LLC 代表美国临床药理学学院出版。

StephenW

Drug-Drug Interactions With the Hepatitis B Virus Capsid Assembly Modulator JNJ-56136379 (Bersacapavir)
Joris Vandenbossche  1 , Jeysen Yogaratnam  2 , Vera Hillewaert  1 , Freya Rasschaert  1 , Willem Talloen  1 , Jeike Biewenga  1 , Jan Snoeys  1 , Thomas N Kakuda  2 , Martyn Palmer  3 , Julius Nangosyah  1 , Michael Biermer  1
Affiliations
Affiliations

    1
    Janssen Pharmaceutica NV, Beerse, Belgium.
    2
    Janssen Research & Development, South San Francisco, California, USA.
    3
    Janssen Research & Development, Spring House, Pennsylvania, USA.

    PMID: 36062869 DOI: 10.1002/cpdd.1164

Abstract

The capsid assembly modulator JNJ-56136379 (bersacapavir) disrupts hepatitis B virus replication. It is metabolized via cytochrome P450 (CYP) 3A, but little is known about the drug-drug interactions of JNJ-56136379 when combined with drugs that inhibit or are metabolized by CYP3A. In a phase 1, open-label trial (NCT03945539), healthy adults received 1 dose of JNJ-56136379 with and without 21 days of prior exposure to itraconazole 200 mg (CYP3A inhibitor). In a second phase 1, open-label trial (NCT03111511), healthy women received 1 dose of drospirenone/ethinyl estradiol and midazolam before and after 15 days of JNJ-56136379. Itraconazole increased the area under the plasma concentration-time curve (AUC) of JNJ-56136379 by 38%. JNJ-56136379 reduced the maximum observed concentration and AUC of midazolam (CYP3A substrate) by 42%-54%, increased AUC of ethinyl estradiol by 1.6-fold, but had no effect on drospirenone pharmacokinetics. Overall, these results demonstrated that a strong CYP3A inhibitor (itraconazole) modestly increased JNJ-56136379 exposure. Furthermore, JNJ-56136379 was a weak inducer of CYP3A (midazolam) and increased ethinyl estradiol exposure; coadministration of high-dose estrogen-based contraceptives and JNJ-56136379 is not recommended.

Keywords: CYP3A; JNJ-56136379; capsid assembly modulator; drug-drug interactions; hepatitis B.

© 2022 The Authors. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.