Effect of formulation on the pharmacokinetics and efficacy of doramectin.
The pharmacokinetics of doramectin, a novel avermectin, were evaluated following parenteral administration in a range of oil-based formulations in an attempt to optimise the formulation. Therapeutic and persistent efficacies against Cooperia oncophora were also evaluated. This approach led to the identification of formulations based upon sesame oil and ethyl oleate which gave more prolonged doramectin plasma concentrations with no loss in therapeutic efficacy and improved persistent efficacy following subcutaneous administration to cattle at a dosage of 200 micrograms kg-1. The importance of using both pharmacokinetic and efficacy end points to distinguish between formulations is discussed. All formulations were well tolerated as evidenced by the absence of any reaction to injection either in the form of behavioural responses, injection site swelling or postmortem lesions. Sesame oil with ethyl oleate was the best parenteral vehicle tested for doramectin, allowing the expression of a high level of therapeutic and persistent efficacy and offering the benefit of excellent injection site toleration.
Wicks
S R
SR
Pfizer Central Research, Sandwich, UK.
Kaye
B
B
Weatherley
A J
AJ
Lewis
D
D
Davison
E
E
Gibson
S P
SP
Smith
D G
DG
D000704:Analysis of Variance; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001682:Biological Availability; D002417:Cattle; D002418:Cattle Diseases / Q000188:drug therapy*; D002626:Chemistry, Pharmaceutical; D004075:Diglycerides; D004337:Drug Carriers; D004341:Drug Evaluation; D005243:Feces / Q000469:parasitology; D007279:Injections, Subcutaneous; D007559:Ivermectin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016014:Linear Models; D008823:Micelles; D009349:Nematode Infections / Q000188:drug therapy / Q000662:veterinary*; D009829:Oleic Acids; D012715:Sesame Oil
D000871:Anthelmintics; D004075:Diglycerides; D004337:Drug Carriers; D008823:Micelles; D009829:Oleic Acids; D007559:Ivermectin; C079597:miglyol 840; D012715:Sesame Oil; C084101:doramectin; C033180:ethyl oleate