Effects of Time of Administration and Posture on the Pharmacokinetics of Cefprozil

Summary

The effects of time of administration, sleep and posture on the pharmacokinetics of cefprozil were evaluated in a single-dose 3-way crossover study. After a 6-hour fast, 12 healthy male volunteers received oral cefprozil 250mg at 1200h (treatment A), 1200h (treatment B) and 2400h (treatment C) with a 7-day washout interval between each treatment. During the study period, volunteers receiving treatment A remained in a sitting/standing position or were ambulatory, those receiving treatment B were in the supine position, and those receiving treatment C were sleeping. Blood samples were taken over an 8-hour period and the plasma samples were analysed for the concentrations of cefprozil by a high performance liquid chromatography-ultraviolet method. Plasma concentration vs time data were analysed using noncompartmental analysis methods.

Mean peak plasma concentrations (C_max) were 4.51, 5.02 and 4.91 mg/L for treatments A, B and C, respectively. Corresponding mean values of the area under the plasma concentration-time curve (AUC_(0−∞)) were 12.6, 12.6 and 14.2 mg/L•h, respectively. The mean half-life (t_½) values were 1.30, 1.23 and 1.50 hours for treatments A, B and C, respectively. Mean AUC_(0−∞), C_max and t½ values following treatment B were not significantly different from those of treatment A. However, the mean AUC_(0−∞) and t_½ values of cefprozil following treatment C were significantly greater than those of either treatment A or B. The mean C_max value following treatment C was not significantly different than that of either treatments A or B.

From these results, it was concluded that posture has no effect on the pharmacokinetics of cefprozil. The administration of cefprozil at night decreases the rate of elimination and thereby increases total exposure to cefprozil. However, the magnitude of the changes in these 2 parameters may not be of any clinical relevance.