The effect of sesame and sunflower oils on the plasma disposition of ivermectin in goats.
The effect of sesame oil (SSO) and sunflower oil (SFO) (the excipients) on the plasma disposition of ivermectin (IVM) following intravenous (i.v.) and subcutaneous (s.c.) administration at a dosage of 200 microg/kg was investigated in goats. Ten clinically healthy crossbred goats were used in the study. The animals were allocated by weight and sex into two groups of five animals each. Group 1 (n = 5) received the drug and excipient by the i.v. route only and group 2 received drug and excipient by the s.c. route only. The study was designed according to a two-phase crossover design protocol. In the first phase three animals in group 1 were i.v. administered IVM (0.2 mg/kg) + SSO (1 mL) and the other two animals received IVM (0.2 mg/kg) + SFO (1 mL). In the second phase animals were crossed over and received the alternate excipient with IVM at the same dosages. In group 2 during the first phase, three animals were s.c. administered IVM (0.2 mg/kg) + SSO (1 mL) and the other two animals were received IVM (0.2 mg/kg) + SFO (1 mL). In the second phase animals were crossed over and received the alternate excipient with IVM at the same dosages. A 4-week washout period was allowed between the two phases. In group 2 significantly increased dermal thickness was observed at the s.c. injection site of the all animals which received IVM during phase I regardless of the excipient. There was almost no change observed at the injection site of any animal during the second phase of the study following s.c. administration. In group 2 the plasma concentrations of IVM in the second phase for both excipient combinations were much higher than the plasma concentrations following first administration and appeared to be related with the dermal changes. The mean plasma disposition of IVM in combination with SSO or SFO was similar following i.v. administration. Longer terminal elimination half-lives and resultant longer mean resident time were observed after s.c. administration of the both combinations compared with i.v. administration.
Gokbulut
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C
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Adnan Menderes, Isikli Koyu, Aydin, Turkey. cengizgokbulut@yahoo.com
Karademir
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U
Boyacioglu
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M
McKellar
Q A
QA
D000704:Analysis of Variance; D000818:Animals; D000977:Antiparasitic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001769:Blood / Q000187:drug effects*; D018592:Cross-Over Studies; D005260:Female; D006041:Goats; D006207:Half-Life; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007559:Ivermectin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D010938:Plant Oils / Q000008:administration & dosage / Q000494:pharmacology*; D012715:Sesame Oil / Q000008:administration & dosage / Q000494:pharmacology*; D000074242:Sunflower Oil
D000977:Antiparasitic Agents; D010938:Plant Oils; D000074242:Sunflower Oil; D007559:Ivermectin; D012715:Sesame Oil