Penetration of cefaclor into the interstitial space fluid of skeletal muscle and lung tissue in rats.
OBJECTIVE
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.
De La Peña
A
A
University of Florida, College of Pharmacy, Department of Pharmaceutics, Gainesville 32610, USA.
Dalla Costa
T
T
Talton
J D
JD
Rehak
E
E
Gross
J
J
Thyroff-Friesinger
U
U
Webb
A I
AI
Müller
M
M
Derendorf
H
H
D000465:Algorithms; D000818:Animals; D002138:Calibration; D002433:Cefaclor / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002511:Cephalosporins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D005110:Extracellular Space / Q000378:metabolism*; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008168:Lung / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D018482:Muscle, Skeletal / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013056:Spectrophotometry, Ultraviolet
D002511:Cephalosporins; D002433:Cefaclor