Lack of Clinically Meaningful Effect of Cariprazine on the Pharmacokinetics of a Combined Oral Contraceptive.

IF 3.9 3区医学 Q1 CLINICAL NEUROLOGY Neurology and Therapy Pub Date : 2025-02-01 Epub Date: 2024-12-19 DOI:10.1007/s40120-024-00686-7

Márta Erzsébet Rosa, Zoltán Juhász, Gabriella Pásztor Mészáros, Gabriella Magyar, Judit Harsányi, Balázs Szatmári, Zoltán Hujber, Máté Szabó, Margit Kapás

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Abstract

Introduction: Cariprazine (CAR) is a potent dopamine receptor partial agonist antipsychotic approved by the EMA and the FDA. To address the uncertainty regarding the effectiveness of hormonal contraceptives during CAR co-administration and whether a second barrier method is necessary, a drug-drug interaction study with an oral contraceptive was conducted post-approval.

Methods: The phase I, fixed-sequence multicenter study involved two periods with 24 patients with schizophrenia, aiming to evaluate the effect of CAR on the pharmacokinetics (PK) of a combined oral contraceptive (COC) containing 30 μg ethinylestradiol (EE) and 150 μg levonorgestrel (LNG). In period A, a single dose of COC alone was administered on day 1. In period B, the highest therapeutic dose of 6 mg CAR was administered once daily from day 4, and a second dose of COC was given concomitantly on day 31.

Results: Overall, CAR had no clinically meaningful effect on the PK of the COC. The terminal half-life and the time of maximum plasma concentration of EE and LNG were not altered by CAR co-administration. The highest difference observed was a decrease of 14% in the maximum plasma concentration of EE, with only slight deviation of the 90% confidence interval (CI) of the test/reference ratio (77.09-96.81) from the generally accepted bioequivalence range of 80-125%, which is not considered clinically relevant. Confidence intervals of all other exposure measures were within the 80-125% range for both EE and LNG.

Conclusions: According to these results, hormonal contraceptives can be considered effective during CAR treatment.

Trial registration: Trial registration number (EudraCT) 2018-003722-80.

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卡立哌嗪对复方口服避孕药药代动力学的影响缺乏临床意义。

Cariprazine （CAR）是EMA和FDA批准的一种有效的多巴胺受体部分激动剂抗精神病药物。为了解决在CAR联合给药期间激素避孕药有效性的不确定性以及是否需要第二屏障方法，在批准后进行了口服避孕药的药物-药物相互作用研究。方法：采用固定顺序的I期多中心研究，纳入2期24例精神分裂症患者，目的是评估CAR对含有30 μg炔雌醇（EE）和150 μg左炔诺孕酮（LNG）的复方口服避孕药（COC）药代动力学（PK）的影响。在A期，在第1天单独给药单剂量COC。在B期，从第4天开始给予最高治疗剂量6mg CAR，每天一次，第31天同时给予第二剂量COC。结果：总体而言，CAR对COC的PK无临床意义的影响。CAR联合给药后，EE和LNG的终末半衰期和最大血浆浓度时间未发生变化。观察到的最大差异是EE的最大血浆浓度下降了14%，试验/参考比（77.09-96.81）的90%置信区间（CI）与普遍接受的80-125%的生物等效性范围只有轻微偏差，这被认为与临床无关。对于EE和LNG，所有其他暴露测量的置信区间均在80-125%范围内。结论：根据这些结果，激素避孕药在CAR治疗中可以被认为是有效的。试验注册：试验注册号（edract） 2018-003722-80。

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

Neurology and Therapy CLINICAL NEUROLOGY-

CiteScore

5.40

自引率

8.10%

发文量

103

审稿时长

6 weeks

期刊介绍： Aims and Scope Neurology and Therapy aims to provide reliable and inclusive, rapid publication for all therapy related research for neurological indications, supporting the timely dissemination of research with a global reach, to help advance scientific discovery and support clinical practice. Neurology and Therapy is an international, open access, peer reviewed, rapid publication journal dedicated to the publication of high-quality clinical (all phases), observational, real-world and health outcomes research around the discovery, development, and use of neurological and psychiatric therapies, (also covering surgery and devices). Studies relating to diagnosis, pharmacoeconomics, public health, quality of life, and patient care, management, and education are also welcomed. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, case reports, trial designs, communications and letters. 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