Premium
A Randomized Crossover Study Investigating the Influence of Ranitidine or Omeprazole on the Pharmacokinetics of Cephalexin Monohydrate
Author(s) -
MadarasKelly Karl,
Michas Patricia,
George Molly,
May Matthew P.,
PhD Adeboye Adejare
Publication year - 2004
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270004269558
Subject(s) - pharmacokinetics , ranitidine , omeprazole , pharmacology , bioequivalence , crossover study , pharmacodynamics , cmax , medicine , drug interaction , proton pump inhibitor , oral administration , chemistry , alternative medicine , pathology , placebo
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 MIC 90 during the dosing interval (T < MIC 90 ) 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 > MIC 90 was observed for cephalexin irrespective of acid suppression. Delay in absorption of cephalexin resulted in a decrease in the percentage of T > MIC 90 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 > MIC 90 .