Penetration of 14C-Ro 13-9904 into tissue cage fluid in rabbits

The pharmacokinetics of Ro 13-9904/001 following i.v. injection of 40 mg/kg was studied in a tissue cage model in rabbits. Binding to rabbit serum proteins was determined by ultrafiltration and found to be 98% at a concentration of 100 microgram/ml. In the early post-injection period concentrations of the drug in rabbit serum reached 500-900 microgram/ml, the antibiotic binding capacity of serum proteins was exceeded and the outflow of drug into the tissues was high. Tissue cage fluid (TCF) concentrations increased during 4h, such as to reach a maximum level of about 30 microgram/ml. After 8 h a t1/2 of 15 h was calculated both in serum and TCF. From 36 h onwards the t1/2 was 75 h. After a single injection of 14C-Ro 13-9904/001 radiological activity could be followed in serum and TCF for 7-10 days and in urine for more than 2 weeks. The results are discussed and compared to those from similar experiments with benzylpenicillin and flucloxacillin.