Pharmacokinetics of Cefixime After Once‐a‐Day and Twice‐a‐Day Dosing to Steady State

Abstract

The pharmacokinetics of cefixime (CL 284,635; FK027), a new orally active broad-spectrum cephalosporin, were determined in 26 healthy volunteers, after multiple 200-mg twice-a-day (group 1; N = 13) or 400-mg once-a-day (group 2; N = 13) dosing for 15 days. On study days 1, 8, and 15, mean peak serum concentrations (C_max) were 1.67, 1.75, and 1.87 μg/mL, respectively, for group 1 and 2.76, 3.04, and 2.67, respectively, for group 2. Over the 15-day period, mean trough serum concentrations were, on average, 0.40 and 0.08 μg/mL for groups 1 and 2, respectively. Comparison (ANOVA) of serum and urinary excretion pharmacokinetic parameters for cefixime on days 1, 8, and 15 found no significant (P > .05) differences for either group except for a small but significantly (P < .05) earlier time to reach C_max and higher renal clearance on days 8 and 15 in group 1. These differences, however, are not clinically significant. On study days 1, 8, and 15, mean C_max and AUC_0-r values for Group 2 were about 1.5 to 2.2 time those for Group 1. Urinary excretion of cefixime accounted for 11.9 to 14.5% and 9.9 to 12.4% of the dose in groups 1 and 2, respectively, over the 15-day study. Overall, there was no accumulation of cefixime in serum or urine nor was there a reduction in serum concentrations or urinary amounts over the 15-day dosing period when the drug was given either as a 200-mg twice-a-day or 400-mg once-a-day dosing regimen.