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 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.
Leppert
P S
PS
INTERx Research, Division of Merck and Company, Lawrence, Kansas 66047.
Cammack
L
L
Cargill
R
R
Coffman
L
L
Cortese
M
M
Engle
K
K
Krupco
C
C
Fix
J A
JA
D000818:Animals; D001672:Biocompatible Materials; D001682:Biological Availability; D002417:Cattle; D002440:Cefoxitin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D003238:Connective Tissue / Q000473:pathology / Q000601:surgery; D004285:Dogs; D005260:Female; D015918:Infusion Pumps, Implantable; D007559:Ivermectin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D008422:Materials Testing; D019736:Prostheses and Implants; D051381:Rats; D017207:Rats, Sprague-Dawley; D012756:Sheep; D013045:Species Specificity; D013193:Stainless Steel; D013997:Time Factors
D001672:Biocompatible Materials; D013193:Stainless Steel; D002440:Cefoxitin; D007559:Ivermectin