Pharmacokinetics of Ceftibuten-cis and Its trans Metabolite in Healthy Volunteers and in Patients with Chronic Renal Insufficiency

Authors

Judy Shepard Kelloway, University of Minnesota
Walid M. Awni, University of Minnesota
Chin C. Lin, Schering-Plough Corporation
Josephine Lim, Schering-Plough Corporation
Melton B. Affrime, Schering-Plough Corporation
William F. Keane, University of Minnesota
Gary R. Matzke, Virginia Commonwealth UniversityFollow
Charles E. Halstenson, University of Minnesota

Document Type

Article

Original Publication Date

1991

Journal/Book/Conference Title

Antimicrobial Agents and Chemotherapy

Volume

35

Issue

11

First Page

2267

Last Page

2274

DOI of Original Publication

10.1128/AAC.35.11.2267

Comments

Originally published at http://dx.doi.org/10.1128/AAC.35.11.2267. At time of publishing, Gary R. Matzke was at University of Minnesota.

Date of Submission

November 2015

Abstract

The impact of renal insufficiency on the dispositions of 300 mg of orally administered ceftibuten-cis, a new broad-spectrum oral cephalosporin, and its primary metabolite ceftibuten-trans was characterized in 30 adult subjects. Subjects were divided into five groups of six subjects each on the basis of their 24-h ambulatory creatinine clearances (CL_CR). The apparent total body clearance (CL_P/F; where F is absolute bioavailability) and renal clearance of ceftibuten-cis were significantly lower in subjects with end-stage renal disease (on maintenance hemodialysis; group V) and in those with severe (CL_CR, 5 to 29 ml/min; group IV) and moderate (CL_CR, 30 to 49 ml/min; group III) renal insufficiency than in those with mild renal insufficiency (CL_CR, 50 to 80 ml/min; group II) or normal renal function (CL_CR, greater than 80 ml/min; group I). A significant correlation was observed between CL_CR and ceftibuten-cis CL_P/F. The mean apparent steady-state volume of distribution (V beta/F) of ceftibuten-cis ranged from 0.21 to 0.24 liter/kg in subjects in group I, II, III, and IV. V beta/F was significantly greater in the group V subjects with end-stage renal disease (V beta/F, 0.39 +/- 0.27 liters/kg). These changes in V beta/F cannot be separated from possible changes in bioavailability. The maximum concentration of ceftibuten-trans in plasma was significantly higher and occurred significantly later in group IV subjects than it did in subjects in the other groups. The terminal elimination half-life of ceftibuten-trans was significantly and progressively prolonged as CL_CR declined (2.63 ± 1.02, 5.37 ± 1.93, 14.29 ± 10.84, and 19.46 ± 9.69 h in groups I, II, III, and IV, respectively). The hemodialysis clearance of ceftibuten-cis was 76.9 ± 18.0 ml/min, and the fraction of the administered dose of ceftibuten-cis removed during ~3 h of hemodialysis-was 39 ±%. Ceftibuten dosage adjustments are proposed for subjects with renal insufficiency.

Rights

Copyright © 1991, the American Society for Microbiology. All rights reserved.

Is Part Of

VCU Pharmacotherapy and Outcomes Science Publications