ELISA determination and preliminary pharmacokinetics of modified human rIL-1 beta in dogs.
A single dose pharmacokinetic study with modified human Interleukin-1 Beta (IL-1 beta or DuP 118) was performed by injecting 5 micrograms/kg of drug into the jugular vein of three beagle dogs. Serial 5-ml plasma samples were removed from the dogs over a 120-minute period. DuP 118 plasma levels were measured using a sandwich ELISA technique capable of measuring concentrations ranging from 0.25 to 2 ng/ml with accuracy and precision constraints of less than +/- 20% variability. DuP 118 stored at -20 degrees C in dog plasma was stable for at least 1 month. Pharmacokinetic parameters were determined for the three dogs by standard model independent or non-compartmental methods. DuP 118 was rapidly distributed in the dog. The volume of distribution was approximately two-fold higher than the total body water of a lean dog. The terminal half-life was short, less than 30 minutes. Within approximately an hour after dosing, DuP 118 plasma levels were reduced 20-fold and were below the quantifiable limit of the assay.
Gray
J E
JE
Drug Metabolism and Pharmacokinetics Section, Du Pont Merck Pharmaceutical Company, Newark, DE 19714.
Peterman
V
V
Newton
R
R
King
S Y
SY
Pieniaszek
H J
HJ
D000818:Animals; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007375:Interleukin-1 / Q000493:pharmacokinetics*; D011817:Rabbits; D011994:Recombinant Proteins / Q000493:pharmacokinetics
D007375:Interleukin-1; D011994:Recombinant Proteins