Pharmacokinetic interactions between ilaprazole and clarithromycin following ilaprazole, clarithromycin and amoxicillin triple therapy

Abstract

Aim: To investigate the drug interactions between ilaprazole, a new proton pump inhibitor, and clarithromycin following ilaprazole, clarithromycin and amoxicillin combination therapy. Methods: Twelve healthy Chinese volunteers were recruited in a randomized, open-label, 3-period crossover study. All subjects were administered ilaprazole (5 mg), clarithromycin (500 mg) or a triple therapy, including ilaprazole (5 mg), clarithromycin (500 mg) and amoxicillin (1 g), twice daily for 6 consecutive days. On the 7th day, the drugs were given once, and blood samples were collected and analyzed using a well-validated HPLC/MS/MS method. Results: Following the triple therapy, the peak concentration (C max ) and the area under the concentration-time curve from 0 h to 12 h (AUC 0→12 ) of ilaprazole were significantly decreased, as compared with the single medication group (C max : 1025.0±319.6 vs 1452.3±324.6 ng/mL; AUC 0→12 : 9777.7±3789.8 vs 11363.1±3442.0 ng· h/mL). Similar changes were found for ilaprazole sulfone (C max : 5.9±0.5 vs 9.3±1.7 ng/mL; AUC 0→12 : 201.4±32.1 vs 277.1±66.2 ng· h/mL). The triple therapy significantly elevated the C max of clarithromycin (3161.5±702.2 vs 2541.9±476.2 ng/mL). Conclusion:The H pylori eradication therapy with clarithromycin, amoxicillin and ilaprazole may cause pharmacokinetic interactions that decrease the amount of ilaprazole and its metabolites and elevate that of clarithromycin.

Biotransformation of Ilaprazole in Human Liver Microsomes and Human: Role of CYP3A4 in Ilaprazole Clearance and Drug-Drug Interaction

“…Therefore, the exposure of rabeprazole to humans is not elevated when clarithromycin is coadministered (Yasuda et al, 1995;Shimizu et al, 2006). We speculated that sulfoxide oxidation to ilaprazole sulfide instead of CYP3A4mediated nonenzymetic sulfoxide reduction to ilaprazole sulfone is the major clearance pathway of ilaprazole in humans, which would explain the observation that the inhibition of CYP3A4 by clarithromycin has not elevated the exposure of ilaprazole to humans (Cao et al, 2012).…”

“…Thus, it has been widely accepted that CYP3A4 plays a major role in the clearance of ilaprazole in humans (Seo et al, 2012;de Bortoli et al, 2013;Shin et al, 2014;Savarino et al, 2016;Wang et al, 2016;Xuan et al, 2016). However, coadministered clarithromycin, a potent CYP3A4 inhibitor, does not elevate the exposure of ilaprazole to human (Cao et al, 2012). The pharmacokinetics of ilaprazole was not affected by CYP3A phenotypes in 24 healthy subjects (Cao et al, 2015).…”

A Sensitive and Specific Indirect Competitive Enzyme-Linked Immunosorbent Assay for Detection of Paeoniflorin and Its Application in Pharmacokinetic Interactions between Paeoniflorin and Glycyrrhizinic Acid

“…1) is the main active component in PR, a monoterpene glycoside with anti-inflammatory, antirheumatic, immunomodulatory [1], analgesic [2], and neuroprotective properties [3]. Several methods are used to determine the concentration of paeoniflorin in medicines and biological samples [4][5][6], with HPLC/MS/MS being the most commonly used method and displaying high sensitivity in pharmacokinetic studies [7][8][9]. The enzyme-linked immunosorbent assay (ELISA) using MAbs is another important method for the qualitative or quantitative detection of these Abstract !…”

Pharmacokinetic drug interaction and safety after coadministration of clarithromycin, amoxicillin, and ilaprazole: a randomised, open-label, one-way crossover, two parallel sequences study

“…CYP2C19 has been revealed to be rarely involved in ilaprazole metabolism unlike that observed for other PPIs such as omeprazole, esomeprazole, pantoprazole, and lansoprazole [ 13 , 19 ]. However, a new metabolite, ilaprazole thiol ether, formed via a non-enzymatic metabolic pathway was identified in human studies after ilaprazole administration, and even ilaprazole thiol ether was detected in large or similar amounts compared to those of ilaprazole sulfone [ 20 , 21 ]. These results indicate that ilaprazole has various metabolic pathways consisting of both CYP-mediated enzymatic and non-enzymatic metabolic pathways, and the non-enzymatic pathway plays a significant role in ilaprazole metabolism.…”