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

doi:10.1016/j.clinthera.2018.06.009

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	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
	Zuo, Cheng-zi 1,2; Gong, Yi 1,2; Hou, Xiang-yu 3; Zhang, Yi-fan3 ; Peng, Wen-xing 1,2; Zhu, Rong-hua 1,2; Zhong, Da-fang3 ; Chen, Xiao-yan3
刊名	CLINICAL THERAPEUTICS
	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.
资助项目	Jiangsu Hengrui Pharmaceutical Co, the developer of imrecoxib[00000000]
WOS关键词	NONSTEROIDAL ANTIINFLAMMATORY DRUGS ; LIVER-MICROSOMES ; METABOLISM ; CELECOXIB ; CYCLOOXYGENASE-2 ; RAT ; INHIBITION ; SAFETY
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	ELSEVIER
WOS记录号	WOS:000444791800012
内容类型	期刊论文
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.