Disposition of cefotaxime and its metabolite, desacetylcefotaxime, in rat: application of a pharmacokinetic-protein binding model
| Autor: | D. W. A. Bourne, E. J. Triggs, Lukman Hakim |
|---|---|
| Rok vydání: | 1989 |
| Předmět: |
Male
Cefotaxime Health Toxicology and Mutagenesis Metabolite Cmax Ultrafiltration Plasma protein binding Biology Pharmacology Toxicology Biochemistry Models Biological chemistry.chemical_compound Pharmacokinetics medicine Animals Binding site Chromatography High Pressure Liquid Serum Albumin Chromatography Rats Inbred Strains General Medicine Metabolism Blood Proteins Rats chemistry Free fraction Spectrophotometry Ultraviolet medicine.drug Protein Binding |
| Zdroj: | Xenobiotica; the fate of foreign compounds in biological systems. 19(7) |
| ISSN: | 0049-8254 |
| Popis: | 1. The pharmacokinetics and protein binding of cefotaxime and desacetylcefotaxime were studied in rat. 2. After i.v. dosing of cefotaxime (100 mg/kg) the concentration-time profiles of cefotaxime and its metabolite desacetylcefotaxime followed biphasic decays, giving the kinetic parameters for cefotaxime: VTss and AUC of 127 ml/kg and 8.2 mg/min per ml, respectively. The beta-elimination half-life was 17 min with Cls of 13.1 ml/min per kg. The average association constant (K x 10(3) M-1) and total protein binding site concentration (Pt x 10(-3) M) for cefotaxime were 3.87 and 0.68, respectively, with saturation of plasma protein binding occurring at about 30 micrograms/ml. The average free fraction of cefotaxime in plasma (Fp) was 0.48. 3. The metabolite desacetylcefotaxime had a plasma Cmax of 74.4 micrograms/ml (35 min). The respective elimination half-life and AUC were 53 min and 7.2 mg/min per ml. The binding profile, unlike that of cefotaxime, was non-saturable with a K value of 13.90M-1. The Fp of desacetylcefotaxime was 0.89. 4. The concentration-time behaviour of total and free desacetylcefotaxime (i.v. bolus, 50 mg/kg) declined biexponentially with respective VTss and AUC of 125 ml/kg and 19.4 mg/min per ml (total drug), and 192 ml/kg and 13.9 mg/min per ml (free drug). The beta-phase half-life of total and free drug was about 36 min, whereas CLs (ml/min per kg) were 2.7 (total) and 3.7 (free). The binding characteristics were in good agreement with those of the metabolite produced in vivo, with a K value of 8.58 M-1. The Fp value of desacetylcefotaxime in plasma was 0.73. |
| Databáze: | OpenAIRE |
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