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

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 (Cmax) 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 Cmax 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 Cmax and AUC0‐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.