INTERSPECIES DIFFERENCES IN SYSTEMIC DRUG AVAILABILITY FOLLOWING SUBCUTANEOUS PULSATILE ADMINISTRATION IN CATTLE, SHEEP, DOGS, AND RATS

Rats, dogs, sheep, and cattle were implanted subcutaneously with stain less-steel tissue cages. Bolus injections of cefoxitin and ivermectin were administered to the interiors of the tissue cages 11, 32, and 60 days after implantation to simulate pulsatile drug release from an imp lanted device. Plasma drug levels were determined for 6 h for cefoxiti n and up to 8 days for ivermectin. Tissue cages were retrieved 3 and 6 months after implantation for macroscopic and microscopic examination . In dogs and rats, plasma levels of both drugs following administrati ons to the tissue cages were significantly lower than those following subcutaneous injection, suggesting that the tissue growth around and i n the cages posed a barrier to systemic drug availability in those spe cies. In cattle and sheep, the tissue cages and associated tissue did not inhibit systemic availability of either drug as compared with rout ine subcutaneous administration. (C) 1994 John Wiley & Sons, Inc.