Distribution of cephalothin and ceftriaxone into experimental interstitial tissue fluid in rabbits

A study was carried out on the access and residence of cephalothin and ceftriaxone in interstitial tissue fluid (ITF) produced experimentally by subcutaneous implantation of spiral steel cages after administration of 30 mg/kg of the two antibiotics to rabbits. The levels reached by the drug in serum and ITF were determined by a microbiological plate diffusion method. The elimination half-lives of cephalothin and ceftriaxone showed mean values of 0.23 and 1.77 h, respectively. Both these values were lower than those found for the disappearance half-lives from ITF. Cephalothin reached a maximum concentration in ITF of 4.37 micrograms/ml at 0.52 h, while ceftriaxone showed a maximum concentration of 24.94 micrograms/ml at 2.09 h. The area under the curve of tissue concentrations of ceftriaxone was approximately 20-fold greater than that of cephalothin at the same dose and using same administration route. The index of the penetration capacity expressed as the quotient of the respective AUC's in ITF and in the systemic circulation gave a value for ceftriaxone which was approximately double that obtained for cephalothin.