PHARMACOKINETICS OF CEFTIBUTEN IN CHILDREN

The bioavailability and pharmacokinetics of ceftibuten administered as an oral suspension were characterized by several studies in young healthy male adults (19 to 39 years old) and children ranging in age from 6 months to 17 years. Ceftibuten suspension was found to be bioequivalent and thus interchangeable with a standard 400-mg capsule, As with the capsule formulation, food slightly (<20%) affected the rate and extent of absorption of the suspension, The recommended dose of 9.0 mg/kg was found to produce comparable plasma concentrations in children of all ages (6 months to 17 years), The range of mean values of maximum plasma concentrations (C-max) was 12 to 16 mu g/ml at the 9.0.mg/kg dose level. Doses of 4.5, 9.0 and 13.5 mg/kg produced C-max and area under the plasma concentration-time curve values that were dose-proportional. The half-life (t(1/2)) was essentially independent of age and dose, ranging from 2 to 3 hours. The apparent clearance (Cl/F), uncorrected for the fraction of drug absorbed (F), is independent of dose but appears to increase with a decrease in age. This also occurs to a lesser degree with the volume of distribution (Vd/F), uncorrected for F. Current evidence suggests that this is more likely to be caused primarily by a decrease in F than an increase in Cl. Ceftibuten rapidly and extensively reaches the middle ear fluid in children with acute otitis media. Within 4 hours concentrations in middle ear fluid are similar to plasma concentrations and can be measured for 12 hours, The ratio of area under the concentration time curve for middle ear fluid relative to plasma was about 70%. The microbiologic and pharmacokinetic characteristics indicate that once or twice daily dosing should be possible for many clinical situations.