Diffusion of cefradine and cefalothin into interstitial fluid of human volunteers with tissue cages

Abstract

For the measurement of antibiotic concentrations, implanted perforated silicone capsules, so-called “tissue cages”, have recently been used in animals, because the fluid obtained from a tissue cage has been shown to have the same characteristics as interstitial tissue fluid and to be in direct communication with other body fluids. The protein content of this fluid is, at 3.99 g/100 ml, relatively low and similar to the interstitial fluid. Whereas all previous studies with tissue cages were done with animals, in this study silicone rubber tissue cages of approximately 35 mm length with 16 perforations were placed in the subcutaneous tissue of the abdomen in human volunteers. The capsules stayed in situ for 3 to 21 days. Specimens were obtained by aspirating fluid from the tissue cage using a syringe and fine needle. The volunteers received a 2 g i. v. dose of cefradine and cefalothin respectively. The concentrations in serum 20 minutes after the infusion was completed were 43.6–84.77 µg/ml with cefradine and 38.4–56 µg/ml with cefalothin. The concentrations in the tissue cage fluid were measured with 10.7 µg/ml in the case of cefradine and 4.8 µg/ml with cefalothin. Twenty-one days after implantation of the chamber the concentrations of cefradine after a 2 g i. v. dose were 20 µg/ml, twice as high as the concentrations in the fluid after three days of implantation. The results obtained show that cefradine, a low protein bound cephalosporine antibiotic, exhibits good diffusion into the tissue cage fluid. The diffusibility of cefalothin, which is protein bound at a higher rate than cefradine, is less. The diffusibility of antibiotics into the tissue cage fluid seems to depend on the protein concentration of the fluid.