Interspecies differences in systemic drug availability following subscutaneous pulsatile administration in cattle, sheep, dogs, and rats

Abstract

Rats, dogs, sheep, and cattle were implanted subcutaneously with stainless-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 implanted device. Plasma drug levels were determined for 6 h for cefoxitin 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 administrations to the tissue cages were significantly lower than those following subcutaneous injection, suggesting that the tissue growth around and in the cages posed a barrier to systemic drug availability in those species. In cattle and sheep, the tissue cages and associated tissue did not inhibit systemic availability of either drug as compared with routine subcutaneous administration.

Design and Testing of an Impedance-Based Sensor for Monitoring Drug Delivery

“…6,7 However, in the case of active devices, where quick pulsatile or more complex release profiles are desired, the isolation of the implant causes a time lag due to the finite amount of time required for diffusion of the drug through the capsule. 8,9 This time delay is also a key factor in the performance of in vivo sensors. 10,11 Even if sensor components are made resistant to the immune response, the sensor must be continually recalibrated to account for the changing conditions in the tissue surrounding it.…”