Daily variations in ceftriaxone pharmacokinetics in rats

The aim of this study was to determine whether the time of day ceftriaxone was administered modified its pharmacokinetics. Ceftriaxone was given intraperitoneally at either 0400, 1000, 1600, and 2200 h to Sprague-Dawley rats synchronized under a light-dark cycle of 12 h of light and 12 h of dark. Pharmacokinetic parameters were analyzed for the presence of a 24-h rhythm. Results showed significant daily variations (P < 0.05) in ceftriaxone clearance, with the highest values during the dark phase. It is concluded that time-dependent variations in ceftriaxone pharmacokinetics may affect the therapeutic efficacy of current once-daily dosing schedules.