Penetration of cefaclor into the interstitial space fluid of skeletal muscle and lung tissue in rats.
Pharm Res
; 18(9): 1310-4, 2001 Sep.
Article
en En
| MEDLINE
| ID: mdl-11683245
ABSTRACT
PURPOSE:
To measure and compare the penetration of cefaclor from the plasma compartment into the interstitial space of lung and skeletal muscle in rats and to integrate the data in a pharmacokinetic model.METHODS:
Unbound interstitial concentrations in muscle and lung were measured by in vivo microdialysis following i.v. bolus doses of 50 and 75 mg/kg cefaclor. Unbound muscle concentrations were also measured after a primed, continuous i.v. infusion at an infusion rate of 0.3 mg/kg/min.RESULTS:
The cefaclor half-life in plasma, muscle and lung was approximately 1 h. Unbound cefaclor concentrations in muscle and lung were found to be virtually identical. A 2-compartment body model was fitted to the data with a tissue penetration factor (AUC(tissue(unbound)))/AUC(plasma(unbound))) of approximately 0.26 independent of dose, tissue and mode of administration.CONCLUSIONS:
Unbound concentrations of cefaclor in the interstitial space fluid of lung and skeletal muscle are of similar magnitude and lower than those in plasma. Using total plasma concentrations would overestimate the antibacterial activity of the drug and therefore its clinical efficacy. Instead, therapeutically active levels of cefaclor at the site of action should be taken into account. Microdialysis allows direct measurement of these unbound concentrations.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Cefaclor
/
Cefalosporinas
/
Músculo Esquelético
/
Espacio Extracelular
/
Pulmón
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Pharm Res
Año:
2001
Tipo del documento:
Article
País de afiliación:
Estados Unidos