Diffusion of beta-lactam antibiotics and fosfomycin to interstitial tissue fluid in rabbits

The ability of seven antibiotics (carbenicillin, cloxacillin, ampicillin, cephalothin, cephaloridine, cefoxitin and fosfomycin) to enter interstitial tissue fluid was evaluated. Using rabbits with implanted subcutaneous chambers, antibiotics were given intramuscularly as a single dose of 15 mg/kg, and antibiotic levels in serum and interstitial fluid of the chambers were determined at variously scheduled times after injection. The results indicated that antibiotic concentrations in the two compartments did not run parallel. The pharmacokinetic analysis showed that, in general, antibiotic diffusion from blood to interstitial fluid increased with the concentration gradient and the serum half-life, and there was an inverse relationship to pKa, protein binding and molecular weight of the antibiotic.