Pharmacokinetic Drug-Drug Interaction between Cilostazol and Rosuvastatin in Healthy Participants.

IF 2.8 4区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS American Journal of Cardiovascular Drugs Pub Date : 2024-11-02 DOI:10.1007/s40256-024-00686-w
Dong Ho Kim, Jang Hee Hong, Won Tae Jung, Kyu-Yeol Nam, Jae Seok Roh, Hye Jung Lee, JungHa Moon, Kyu Yeon Kim, Jin-Gyu Jung, Jung Sunwoo
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Abstract

Background and objectives: Cilostazol improves ischemic symptoms and prevents recurrence following cerebral infarction, and rosuvastatin reduces cholesterol levels. However, no reports exist on the pharmacokinetic interactions between these two drugs in healthy adults. This study evaluated the pharmacokinetic (PK) interactions and safety of cilostazol and rosuvastatin when co-administered to healthy male participants.

Methods: A randomized, open-label, multiple-dosing, two-arm, two-period study was conducted. Arm A had 30 participants receiving 200 mg cilostazol daily and arm B had 27 participants receiving 20 mg rosuvastatin daily for 7 days. In period 2, both arms received a combination of 200 mg cilostazol and 20 mg rosuvastatin daily for 7 days following a 7-day washout period. Plasma concentrations of cilostazol, its metabolites, and rosuvastatin were quantified using liquid chromatography-tandem mass spectrometry.

Results: Fifty-seven participants were randomized, and 44 completed the study. The geometric mean ratio (GMR) and 90% confidence intervals (CI) for maximum plasma concentration at steady state (Cmax,ss) and area under the plasma concentration-time curve during the dosing interval at steady state (AUCtau,ss) indicated no significant interaction between cilostazol and rosuvastatin. Safety assessments showed comparable profiles to individual drug administration, with no significant adverse events.

Conclusion: The repeated co-administration of cilostazol and rosuvastatin in healthy male participants resulted in minor PK interactions and exhibited a safety and tolerability profile similar to those of the individual drugs. This suggested that the combined regimen is well tolerated and does not necessitate dose adjustments.

Registration: ClinicalTrials.Gov identifier no. NCT06568133.

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健康参与者体内西洛他唑与瑞舒伐他汀之间的药代动力学药物相互作用
背景和目的:西洛他唑可改善脑梗塞后的缺血性症状并预防复发,洛伐他汀可降低胆固醇水平。然而,目前还没有关于这两种药物在健康成人中的药代动力学相互作用的报道。本研究评估了健康男性服用西洛他唑和罗伐他汀时的药代动力学(PK)相互作用和安全性:研究采用随机、开放标签、多剂量、双臂、两阶段的方法。A组有30名参与者,每天服用200毫克西洛他唑,B组有27名参与者,每天服用20毫克罗伐他汀,连续服用7天。在第二期研究中,两组受试者均在 7 天的冲洗期后每天接受 200 毫克西洛他唑和 20 毫克罗伐他汀的联合治疗。采用液相色谱-串联质谱法对西洛他唑、其代谢物和罗伐他汀的血浆浓度进行定量分析:57 名参与者被随机分配,其中 44 人完成了研究。稳定状态下最大血浆浓度(Cmax,ss)和稳定状态下给药间隔期间血浆浓度-时间曲线下面积(AUCtau,ss)的几何平均比(GMR)和90%置信区间(CI)显示,西洛他唑和罗伐他汀之间没有显著的相互作用。安全性评估显示,西洛他唑和罗伐他汀的安全性与单独用药相当,没有出现明显的不良反应:结论:在健康男性参试者中重复联合使用西洛他唑和罗伐他汀会产生轻微的 PK 相互作用,其安全性和耐受性与单个药物相似。这表明联合用药的耐受性良好,无需调整剂量:注册:ClinicalTrials.Gov 识别码编号:NCT06568133。NCT06568133。
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来源期刊
CiteScore
6.70
自引率
3.30%
发文量
38
审稿时长
>12 weeks
期刊介绍: Promoting rational therapy within the discipline of cardiology, the American Journal of Cardiovascular Drugs covers all aspects of the treatment of cardiovascular disorders, particularly the place in therapy of newer and established agents. Via a program of reviews and original clinical research articles, the journal addresses major issues relating to treatment of these disorders, including the pharmacology, efficacy and adverse effects of the major classes of drugs; information on newly developed drugs and drug classes; the therapeutic implications of latest research into the aetiology of cardiovascular disorders; and the practical management of specific clinical situations. The American Journal of Cardiovascular Drugs offers a range of additional enhanced features designed to increase the visibility, readership and educational value of the journal’s content. Each article is accompanied by a Key Points summary, giving a time-efficient overview of the content to a wide readership. Articles may be accompanied by plain language summaries to assist patients, caregivers and others in understanding important medical advances. The journal also provides the option to include various other types of enhanced features including slide sets, videos and animations. All enhanced features are peer reviewed to the same high standard as the article itself. Peer review is conducted using Editorial Manager®, supported by a database of international experts. This database is shared with other Adis journals.
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