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A Randomized Crossover Study Investigating the Influence of Ranitidine or Omeprazole on the Pharmacokinetics of Cephalexin Monohydrate

From the Department of Veterans Affairs Medical Center, Boise, Idaho (Dr Madaras-Kelly, Ms Michas, Ms George); the College of Pharmacy, Idaho State University, Pocatello, Idaho (Dr Madaras-Kelly, Mr May); and Philadelphia College of Pharmacy, University of the Sciences in Philadelphia, Philadelphia, Pennsylvania (Dr Adejare).

Limited data characterize pharmacokinetic interactions between cephalexin and ranitidine, and no data exist for an interaction with proton pump inhibitors. The purpose of this study was to investigate the effects of ranitidine or omeprazole administration on the pharmacokinetics and pharmacodynamics of cephalexin. A randomized single- and multiple-dose crossover study was conducted in healthy subjects ingesting cephalexin before and after steady-state administration of ranitidine or omeprazole. Time-concentration profiles were determined and pharmacokinetic parameters were characterized using noncompartmental methods. Pharmacokinetic data were analyzed in accordance with the two 1-sided test for bioequivalence. The percentage of time that serum concentrations remain above the MIC₉₀ during the dosing interval (T > MIC₉₀) for Streptococcus pyogenes and Staphylococcus aureus associated with the pharmacokinetic profiles was calculated. The coadministration of cephalexin with ranitidine or omeprazole resulted in relatively minor changes in C_max, AUC, t_1/2, or CL/F. t_max was significantly prolonged when cephalexin was administered with ranitidine or omeprazole. Suboptimal T > MIC₉₀ was observed for cephalexin irrespective of acid suppression. Delay in absorption of cephalexin resulted in a decrease in the percentage of T > MIC₉₀ for certain acid-suppressive regimens and pathogen combinations. With the exception of an increase in t_max, there were no significant pharmacokinetic interactions between cephalexin and ranitidine or omeprazole. Delayed t_max associated with acid suppression may result in a diminished T > MIC₉₀.

Key Words: Cephalexin • ranitidine • omeprazole • drug interactions • pharmacokinetics

Address for reprints: Karl Madaras-Kelly, PharmD, ISU College of Pharmacy, c/o Boise VA Medical Center, 500 W. Fort Street (119A), Boise, ID 83702.

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