Chemical formula: C₁₅H₁₄N₄O₆S₂ Molecular mass: 410.425 g/mol PubChem compound: 5282242
Ceftibuten is rapidly absorbed after oral administration of capsules. When ceftibuten Capsules were administered once daily for 7 days, the average Cmax was 17.9 µg/mL on day 7. Therefore, ceftibuten accumulation in plasma is about 20% at steady state.
The absolute bioavailability of ceftibuten oral suspension has not been determined. The plasma concentrations of ceftibuten in pediatric patients are dose proportional following single doses of ceftibuten capsules of 200 mg and 400 mg and of ceftibuten oral suspension between 4.5 mg/kg and 9 mg/kg.
The average apparent volume of distribution (V/F) of ceftibuten in 6 adult subjects is 0.21 L/kg (± 1 SD = 0.03 L/kg).
The average apparent volume of distribution (V/F) of ceftibuten in 32 fasting pediatric patients is 0.5 L/kg (± 1 SD = 0.2 L/kg).
Ceftibuten is 65% bound to plasma proteins. The protein binding is independent of plasma ceftibuten concentration.
In a study of 15 adults administered a single 400-mg dose of ceftibuten and scheduled to undergo bronchoscopy, the mean concentrations in epithelial lining fluid and bronchial mucosa were 15% and 37%, respectively, of the plasma concentrations.
Ceftibuten sputum levels average approximately 7% of the concomitant plasma ceftibuten level. In a study of 24 adults administered ceftibuten 200 mg bid or 400 mg qd, the average Cmax in sputum (1.5 µg/mL) occurred at 2 hours postdose and the average Cmax in plasma (17 µg/mL) occurred at 2 hours postdose.
In a study of 12 pediatric patients administered 9 mg/kg, ceftibuten MEF area under the curve (AUC) averaged approximately 70% of the plasma AUC. In the same study, Cmax values were 14.3 ± 2.7 µg/mL in MEF at 4 hours postdose and 14.5 ± 3.7 µg/mL in plasma at 2 hours postdose.
Data on ceftibuten penetration into tonsillar tissue are not available.
Data on ceftibuten penetration into cerebrospinal fluid are not available.
A study with radiolabeled ceftibuten administered to 6 healthy adult male volunteers demonstrated that cis-ceftibuten is the predominant component in both plasma and urine. About 10% of ceftibuten is converted to the trans-isomer. The trans-isomer is approximately ⅛ as antimicrobially potent as the cis-isomer. Ceftibuten is excreted in the urine; 95% of the administered radioactivity was recovered either in urine or feces. In 6 healthy adult male volunteers, approximately 56% of the administered dose of ceftibuten was recovered from urine and 39% from the feces within 24 hours. Because renal excretion is a significant pathway of elimination, patients with renal dysfunction and patients undergoing hemodialysis require dosage adjustment.
Food affects the bioavailability of ceftibuten from capsules and oral suspension.
The effect of food on the bioavailability of capsules was evaluated in 26 healthy adult male volunteers who ingested 400 mg of capsules after an overnight fast or immediately after a standardized breakfast. Results showed that food delays the time of Cmax by 1.75 hours, decreases the Cmax by 18%, and decreases the extent of absorption (AUC) by 8%.
The effect of food on the bioavailability of oral suspension was evaluated in 18 healthy adult male volunteers who ingested 400 mg of oral suspension after an overnight fast or immediately after a standardized breakfast. Results obtained demonstrated a decrease in Cmax of 26% and an AUC of 17% when oral suspension was administered with a high-fat breakfast, and a decrease in Cmax of 17% and an AUC of 12% when oral suspension was administered with a low-calorie nonfat breakfast.
A study in 18 healthy adult male volunteers demonstrated that a 400-mg dose of capsules produced equivalent concentrations to a 400-mg dose of oral suspension. Average Cmax values were 15.6 (3.1) µg/mL for the capsule and 17.0 (3.2) µg/mL for the suspension. Average AUC values were 80.1 (14.4) µg∙hr/mL for the capsule and 87.0 (12.2) µg∙hr/mL for the suspension.
Ceftibuten pharmacokinetics have been investigated in elderly (65 years of age and older) men (n=8) and women (n=4). Each volunteer received ceftibuten 200 mg capsules twice daily for 31/2 days. The average Cmax was 17.5 (3.7) µg/mL after 31/2 days of dosing compared to 12.9 (2.1) µg/mL after the first dose; ceftibuten accumulation in plasma was 40% at steady state. Information regarding the renal function of these volunteers was not available; therefore, the significance of this finding for clinical use of capsules in elderly patients is not clear. Ceftibuten dosage adjustment in elderly patients may be necessary.
Ceftibuten pharmacokinetics have been investigated in adult patients with renal dysfunction. The ceftibuten plasma half-life increased and apparent total clearance (CI/F) decreased proportionately with increasing degree of renal dysfunction. In 6 patients with moderate renal dysfunction (creatinine clearance 30 to 49 mL/min), the plasma half-life of ceftibuten increased to 7.1 hours and CI/F decreased to 30 mL/min. In 6 patients with severe renal dysfunction (creatinine clearance 5 to 29 mL/min), the half-life increased to 13.4 hours and CI/F decreased to 16 mL/min. In 6 functionally anephric patients (creatinine clearance <5 mL/min), the half-life increased to 22.3 hours and CI/F decreased to 11 mL/min (a 7- to 8-fold change compared to healthy volunteers). Hemodialysis removed 65% of the drug from the blood in 2 to 4 hours. These changes serve as the basis for dosage adjustment recommendations in adult patients with mild to severe renal dysfunction.
Ceftibuten exerts its bactericidal action by binding to essential target proteins of the bacterial cell wall. This binding leads to inhibition of cell-wall synthesis.
Ceftibuten is stable in the presence of most plasmid-mediated beta-lactamases, but it is not stable in the presence of chromosomally-mediated cephalosporinases produced in organisms such as Bacteroides, Citrobacter, Enterobacter, Morganella, and Serratia.
Like other beta-lactam agents, ceftibuten should not be used against strains resistant to beta-lactams due to general mechanisms such as permeability or penicillin-binding protein changes like penicillin-resistant S. pneumoniae.
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