Effect of Fluconazole on the Pharmacokinetic Properties of Imrecoxib, a Novel NSAID: A Single-center, Open-label, Self-controlled Study in Healthy Chinese Male Volunteers
文献类型：期刊论文
| 作者 | Zuo, Cheng-zi1,2; Gong, Yi1,2; Hou, Xiang-yu3; Zhang, Yi-fan3 ; Peng, Wen-xing1,2; Zhu, Rong-hua1,2; Zhong, Da-fang3; Chen, Xiao-yan3
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| 刊名 | CLINICAL THERAPEUTICS
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| 出版日期 | 2018-08 |
| 卷号 | 40期号:8页码:1347-1356 |
| 关键词 | COX-2 inhibitor drug interaction fluconazole imrecoxib pharmacokinetics NASID |
| ISSN号 | 0149-2918 |
| DOI | 10.1016/j.clinthera.2018.06.009 |
| 文献子类 | Article |
| 英文摘要 | Purpose: Imrecoxib is one type of cyclooxygenase-2 inhibitor with the capability of reducing the potential cardiovascular risk caused by other NSAIDs. Co-administration with other medications can affect the cytochrome P450 (CYP) 2C9 enzyme function; thus, imrecoxib metabolism can be affected. The purpose of this research was to evaluate the effects of fluconazole, which is known to inhibit CYP2C9, on imrecoxib's pharmacokinetic (PK) parameters. Methods: In this single-center, single-arm, open label, self-controlled study, 12 healthy Chinese male volunteers (mean [SD] age, 22.6 [2.43] years) received the following 2 treatments separated by a washout period of 8 days under a fasting state: (1) a single oral dose of imrecoxib 100 mg; and (2) fluconazole 200 mg/d over 6 days followed by concurrent dosing of imrecoxib 100 mg and fluconazole 200 mg. Plasma concentrations of imrecoxib (MO) and its metabolites (4'-hydroxymethyl metabolite [M1] and 4'-carboxylic acid metabolite [M2]) for PK analysis were obtained at 0 (baseline) and 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 48, and 72 hours after imrecoxib dosing. Safety and toler-ability assessments were performed throughout the study. Findings: All subjects completed the study. There was 1 adverse event; drug-induced liver damage in 1 subject occurred after he received imrecoxib plus fluconazole, and the subject recovered without any sequelae. Coadministration with fluconazole resulted in much higher plasma imrecoxib concentrations, with an increase of 88% in C-max and 72% in AUC(0-t) compared with only imrecoxib treatment, which showed that fluconazole may increase plasma exposure to imrecoxib. Fluconazole also caused a small, but not clinically relevant, decrease in M1 and M2 mean C-max (13% and 14%, respectively), but there was minimal change in M1 and M2 mean AUC(0-t) (3% and 2%). However, there were no statistically significant differences in vital signs, clinical laboratory test results, ECGs, or adverse events between treatments. (C) 2018 Elsevier Inc. All rights reserved. |
| WOS关键词 | NONSTEROIDAL ANTIINFLAMMATORY DRUGS ; LIVER-MICROSOMES ; METABOLISM ; CELECOXIB ; CYCLOOXYGENASE-2 ; RAT ; INHIBITION ; SAFETY |
| 资助项目 | Jiangsu Hengrui Pharmaceutical Co, the developer of imrecoxib[00000000] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000444791800012 |
| 出版者 | ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279632]  |
| 专题 | 上海药物代谢研究中心 |
| 通讯作者 | Peng, Wen-xing; Chen, Xiao-yan |
| 作者单位 | 1.Cent S Univ, Xiangya Hosp 2, Dept Pharm, 139 Middle Renmin Rd, Changsha 410011, Hunan, Peoples R China; 2.Cent S Univ, Inst Clin Pharm, Changsha 410011, Hunan, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zuo, Cheng-zi,Gong, Yi,Hou, Xiang-yu,et al. Effect of Fluconazole on the Pharmacokinetic Properties of Imrecoxib, a Novel NSAID: A Single-center, Open-label, Self-controlled Study in Healthy Chinese Male Volunteers[J]. CLINICAL THERAPEUTICS,2018,40(8):1347-1356. |
| APA | Zuo, Cheng-zi.,Gong, Yi.,Hou, Xiang-yu.,Zhang, Yi-fan.,Peng, Wen-xing.,...&Chen, Xiao-yan.(2018).Effect of Fluconazole on the Pharmacokinetic Properties of Imrecoxib, a Novel NSAID: A Single-center, Open-label, Self-controlled Study in Healthy Chinese Male Volunteers.CLINICAL THERAPEUTICS,40(8),1347-1356. |
| MLA | Zuo, Cheng-zi,et al."Effect of Fluconazole on the Pharmacokinetic Properties of Imrecoxib, a Novel NSAID: A Single-center, Open-label, Self-controlled Study in Healthy Chinese Male Volunteers".CLINICAL THERAPEUTICS 40.8(2018):1347-1356. |
入库方式： OAI收割
来源：上海药物研究所
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