Imrecoxib: Advances in Pharmacology and Therapeutics

Figures & data

Figure 1 Flow chart showing selection of literature.

Table 1 List of Coxibs in Terms of Pharmacokinetics and Pharmacodynamics

Items	Celecoxib	Etoricoxib	Rofecoxib	Imrecoxib	Valdecoxib	Lumiracoxib
Chemical structure	Sulfonamides	Methylsulphones	Methylsulphones	Methylsulphones	Sulfonamides	Phenylacetic acid derivative
COX-1/COX-2 IC50 ratio	7.6	106	35	6.39	30	515
Market status	Available	Available (not approved by the FDA)	Withdrawn in September 2004	Available	Withdrawn in April 2005	Withdrawn from the Canadian, Australian and EMEA market due to concerns that it may cause liver failure
Drug metabolism	Eliminated by hepatic metabolism involving mainly CYP2C9.	Eliminated by hepatic metabolism involving mainly CYP3A4.	Eliminated predominantly by hepatic metabolism primarily through reduction by cytosolic enzymes.	Eliminated by hepatic metabolism involving CYP2C9 (62.5%), CYP2D6 (21.1%), and CYP3A4 (16.4%).	Eliminated by extensive hepatic metabolism involving CYP3A4, CYP2C9, and glucuronidation.	Eliminated by hepatic metabolism involving mainly CYP2C9.
Drug interaction potential	Celecoxib is a CYP2D6 inhibitor.	No inhibitory effects on CYP2C9, 2C19, 2D6, 2E1 or 3A4 are expected to occur with etoricoxib.	Rofecoxib is a potent, metabolism-dependent inhibitor of CYP1A2	Imrecoxib is a weak inhibitory effect on CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4.	Valdecoxib is not a significant inhibitor of CYP1A2, 3A4, 2D6 and CYP2C9 and a weak to moderate inhibitor of CYP 2C19.	Lumiracoxib does not exhibit any clinically meaningful interactions with commonly used medications.
Elimination half-life	11 ~ 16 h	19~32 h	17 h	20 h (M1: 26.0 h; M2: 15.7 h)	8~11 h	5~ 8 h
Genetic polymorphism in drug metabolism	CYP2C9 genotype affects the clearance of celecoxib, and personalized dosing based on CYP2C9 phenotype is necessary.	CYP2C9 plays a relatively minor role in the overall clearance.	CYP2C9 plays a relatively minor role in the overall clearance.	It has not been reported yet, but CYP2C9 genotype appears to have limited influence on the pharmacokinetics of imrecoxib.	CYP2C9 genotype is expected to affect the clearance.	The pharmacokinetics of lumiracoxib is not significantly impacted by CYP2C9 genetic variants in vivo.

Abbreviations: CYP, cytochrome P450; COX, cyclooxygenase; EMEA, The European Medicines Agency; IC50, the concentration at which an non-steroidal anti-inflammatory drug produces 50% inhibition of COX-1 and/or COX-2.

Figure 2 Chemical structures of COX-2 inhibitors.