Pharmacokinetics and bioequivalence of parenterally administered doramectin in cattle.
Plasma concentrations of doramectin in 40 cattle dosed by subcutaneous (sc) or intramuscular (i.m.) injection (200 micrograms/kg) were compared to assess the bioequivalence of the two routes of administration. Peak concentration (Cmax), and areas under the concentration curve (AUC0-infinity) were determined from plasma concentrations. Animals treated by the sc route showed a mean AUC0-infinity of 457 +/- 66 ng.day/mL (+/- SD) and a mean Cmax of 27.8 +/- 7.9 ng/mL. Results from the i.m. treatment group showed a mean AUC0-infinity of 475 +/- 82 ng.day/mL and a mean Cmax of 33.1 +/- 9.0 ng/mL. Absorption constants (ka) determined by modelling were 0.542 +/- 0.336 day-1 after sc administration and 0.710 +/- 0.357 day-1 after i.m. administration. The 90% confidence limits on the difference between mean AUC0-infinity values for the sc and i.m. groups fell within 20% of the mean value for the subcutaneous group. Cmax was somewhat greater for the i.m. route. The 90% confidence limits on the difference in mean In(Tmax +1) also fell within 20% of the mean sc value. Based on this analysis, bioequivalence of the sc and i.m. formulation has been established.
Nowakowski
M A
MA
Pfizer Inc. Central Research Division, Groton, Connecticut 06340, USA.
Lynch
M J
MJ
Smith
D G
DG
Logan
N B
NB
Mouzin
D E
DE
Lukaszewicz
J
J
Ryan
N I
NI
Hunter
R P
RP
Jones
R M
RM
D000042:Absorption; D000704:Analysis of Variance; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002417:Cattle / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006207:Half-Life; D007273:Injections, Intramuscular / Q000662:veterinary; D007279:Injections, Subcutaneous / Q000662:veterinary; D007559:Ivermectin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D008297:Male; D012015:Reference Standards; D013810:Therapeutic Equivalency
D000871:Anthelmintics; C098208:UK 71647; D007559:Ivermectin; C084101:doramectin