title: Effect of clarithromycin and other macrolides on the sulfoxidation and 5-hydroxylation of lansoprazole in dogs.
abstract: The purpose of this study was to evaluate a possible interaction between lansoprazole and clarithromycin as well as other macrolides in dogs. Lansoprazole (30 mg) was orally administered to male beagle dogs, with or without oral pretreatment with 200-mg clarithromycin twice a day for 5 d. The experiments had a randomized cross-over design with a two-week washout period between dosing regimens. Clarithromycin pretreatment for 5 d resulted in a significant increase in the area under the serum lansoprazole concentration-time curve (AUC), whereas the area for a lansoprazole metabolite, lansoprazole sulfone, was significantly reduced, as was the maximum serum concentration (Cmax) of lansoprazole sulfone. When the effects of clarithromycin on the metabolism of lansoprazole were studied using dog liver microsomes, it was found that clarithromycin significantly inhibited the formation of lansoprazole sulfone but not another metabolite, 5-hydroxylansoprazole. These results suggest that co-medication of lansoprazole with clarithromycin may produce a synergistic effect caused by the increased serum levels of lansoprazole of benefit in Helicobacter pylori eradication.
authors.affiliation: Department of Pharmacy, Kumamoto University Hospital, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Masa
authors.forename: K
authors.initials: K
authors.lastname: Arimori
authors.forename: T
authors.initials: T
authors.lastname: Nakayama
authors.forename: S
authors.initials: S
authors.lastname: Miyamoto
authors.forename: J
authors.initials: J
authors.lastname: Fujii
authors.forename: M
authors.initials: M
authors.lastname: Nakano
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000897:Anti-Ulcer Agents / Q000378:metabolism* / Q000493:pharmacokinetics; D017291:Clarithromycin / Q000494:pharmacology*; D004285:Dogs; D004347:Drug Interactions; D006900:Hydroxylation; D066298:In Vitro Techniques; D064747:Lansoprazole; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000900:Anti-Bacterial Agents; D000897:Anti-Ulcer Agents; D064747:Lansoprazole; C581535:Lansoprazole Sulfone; D017291:Clarithromycin; D009853:Omeprazole