Ceftibuten pharmacokinetics and pharmacodynamics. Focus on paediatric use.
Ceftibuten is an extended-spectrum, cephem antimicrobial agent formulated for oral administration. Ceftibuten is absorbed by carrier-mediated processes and passive diffusion. The absorption of ceftibuten is described adequately by a first-order process. Following oral administration, peak serum ceftibuten concentrations are reached within 2 to 3 hours. Although the absolute bioavailability of ceftibuten in humans is not known, its relative bioavailability indicates that there is relatively rapid and complete absorption of the drug. Administration of ceftibuten with food may decrease the rate of absorption and, in the case of high fat meals, may decrease the extent of absorption by approximately 20 to 30%. The results of limited studies indicate that the drug distributes well into various body tissues and fluids, with relatively high concentrations being achieved in organs that receive a significant portion of the cardiac output. In adults with normal renal function or chronic renal failure, the apparent volume of distribution (Vd/F) for ceftibuten ranges from 0.2 to 0.4 L/kg and the total plasma clearance (CL/F) ranges from approximately 61 to 75 ml/min (3.7 to 4.5 L/h). Studies of ceftibuten elimination in adults have demonstrated positive linear correlation between CL/F and creatinine clearance. Following administration of a single dose of ceftibuten, approximately 67 to 94% of the drug has been recovered in the urine unchanged. The elimination half-life (t1/2 beta) of ceftibuten in adults with normal renal function is approximately 2.5 hours. Significant accumulation of ceftibuten does not occur with repeated administration. Despite the fact that the mean time taken to achieve maximal serum concentration (tmax) [1.1 to 2 hours] and t1/2 beta (2.1 hours) following administration of a single dose of ceftibuten to infants and children were similar to values previously reported in adults, the Vd/F (0.42 L/kg) and CL/F (3.1 ml/h/kg) were considerably greater in children younger than 5 years. Additionally, the apparent nonrenal clearance of ceftibuten in paediatric patients (52% of CL/F) was greater than reported for adults (approximately 32% of CL/F) with normal renal function. Thus, developmental differences appear to affect the pharmacokinetic profile of ceftibuten. Ceftibuten has a wide spectrum of antimicrobial activity against both Gram-positive and Gram-negative pathogens, and is stable to hydrolysis by a large number of beta-lactamases. Notable exceptions with regard to the Gram-positive spectrum for ceftibuten include relative or documented resistance for most strains of Listeria, Staphylococcus aureus, S. epidermidis, penicillin-resistant strains of Streptococcus pneumonia and S. enterococcus.(ABSTRACT TRUNCATED AT 400 WORDS)
Kearns
G L
GL
Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock.
Young
R A
RA
D000293:Adolescent; D000328:Adult; D000375:Aging / Q000378:metabolism; D000818:Animals; D001419:Bacteria / Q000187:drug effects; D001682:Biological Availability; D000077722:Ceftibuten; D002511:Cephalosporins / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004347:Drug Interactions; D006801:Humans; D007223:Infant; D007408:Intestinal Absorption; D008826:Microbial Sensitivity Tests; D010033:Otitis Media / Q000188:drug therapy; D010372:Pediatrics; D012141:Respiratory Tract Infections / Q000188:drug therapy; D014018:Tissue Distribution
D002511:Cephalosporins; D000077722:Ceftibuten