title: Multiple-dose pharmacokinetics of ceftibuten after oral administration to healthy volunteers.
abstract: The pharmacokinetics of ceftibuten in plasma and urine were investigated after oral administration. Twelve healthy subjects were treated orally twice daily with 400 mg of the drug for 7 days; on day 8, the subjects received a last dose of 400 mg of ceftibuten. Ceftibuten and its metabolite, the trans isomer of ceftibuten, were assayed in plasma and urine by a specific HPLC method with UV detection. Ceftibuten was rapidly absorbed, as evidenced by the mean time to the maximum observed cis-ceftibuten concentration of 2.4 h. To describe the drug intake process, a Weibull model was used. For the metabolite, the mean time to maximum concentration in plasma was 3.25 h. Mean values for the terminal half-life in plasma were 2.17 h for cis-ceftibuten and 3.19 h for trans-ceftibuten. The overall elimination half-life, tmax, and total and renal clearances of cis-ceftibuten were invariant with respect to duration of dosing. The area under the plasma concentration versus time curve from 0 to infinity and the Cmax of this drug were significantly higher on day 8 than the values predicted from the elimination half-life computed on day 1 of treatment and the dosing interval. The pharmacokinetic parameters of trans-ceftibuten were invariant with respect to duration of dosing. Ceftibuten was well tolerated; there were no clinically significant adverse clinical events. The results from the present study indicate that the levels of cis-ceftibuten in plasma as well as in urine remain above the MICs for susceptible organisms over the dosing interval.
authors: Laboratoire de Pharmacocinétique, Hôpital Carémeau, Nîmes.
authors: F
authors: F
authors: Bressolle
authors: M
authors: M
authors: Galtier
authors: J M
authors: JM
authors: Kinowski
authors: F
authors: F
authors: Goncalves
authors: L
authors: L
authors: Edno
authors: R
authors: R
authors: Panis
authors: R
authors: R
authors: Gomeni
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D002214:Capsules; D000077722:Ceftibuten; D002511:Cephalosporins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D006801:Humans; D008297:Male; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism
chemical_list: D002214:Capsules; D002511:Cephalosporins; D000077722:Ceftibuten