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Comparative pharmacokinetics of levamisole-oxyclozanide combination in sheep and goats following per os administration
2014
Gokbulut, Cengiz | Yalinkilinc, Hande Sultan | Aksit, Dilek | Veneziano, Vincenzo
Since there is no registered anthelmintic drug available for use in goats, extra-label use of drugs is a common practice in most countries. The aim of the present study was to compare the pharmacokinetic disposition of levamisole (LVM)-oxyclozanide (OXZ) combination in sheep and goats following per osadministration. Goats (n= 8) and sheep (n= 8) 12- to 16-months-old were used for this study. The animals received tablet formulation of LVM and OXZ combination orally at a dose of 7.5 mg/kg and 15 mg/kg body weight, respectively. Blood samples were collected by jugular vein at different times between 5 min and 120 h after drug administrations. The plasma concentrations of LVM and OXZ were analyzed by HPLC following liquid-liquid phase extraction procedures. The plasma concentrations and systemic availabilities of both LVM and OXZ in goats were lower and the plasma persistence of LVM was shorter compared with those observed in sheep. Terminal half-lives (t1/2-z) of both molecules are shorter in goats compared with those in sheep. Goats treated with LVM-OXZ combination at the recommended dose for sheep may result in a reduced efficacy, because of under-dosing, which may increase the risk of drug resistance in parasites. Increased or repeated dose could be a strategy to provide higher plasma Concentration and thus to improve the efficacy against the target parasites in goats compared with sheep. However, some adverse reactions may occur since LVM has relatively very narrow therapeutic index due to its nicotine-like structure and effect.
Show more [+] Less [-]Pharmacokinetics of ceftiofur crystalline-free acid following subcutaneous administration of a single dose to sheep
2014
Rivera-Garcia, Sarai | Angelos, John A. | Rowe, Joan D. | Byrne, Barbara A. | Wetzlich, Scott E. | Van Liew, Dana B. | Tell, Lisa A.
Objective-To determine the pharmacokinetics of ceftiofur crystalline-free acid (CCFA) following SC administration of a single dose to sheep. Animals-9 healthy adult female Suffolk-crossbred sheep. Procedures-Each sheep was administered 6.6 mg of CCFA/kg, SC, in the cervical region once. Serial blood samples were collected at predetermined intervals for 14 days. Serum concentration of ceftiofur free-acid equivalents (CFAE) was determined by high-performance liquid chromatography. Pharmacokinetic parameters were determined by compartmental and noncompartmental methods. Results-Pharmacokinetics for CCFA following SC administration in sheep was best described with a 1-compartment model. Mean +/- SD area under the concentration-time curve from time 0 to infinity, peak serum concentration, and time to peak serum concentration were 206.6 +/- 24.8 μ•h/mL, 2.4 +/- 0.5 μg/mL, and 23.1 +/- 10.1 h, respectively. Serum CFAE concentrations ≥ 1 μg/mL (the target serum CFAE concentration for treatment of disease caused by Mannheimia haemolytica and Pasteurella multocida) were maintained for 2.6 to 4.9 days. No significant adverse reactions to CCFA administration were observed. Conclusions and Clinical Relevance-Results indicated that adequate therapeutic serum concentrations of CFAE for treatment of disease caused by M haemolytica and P multocida were achieved in sheep following SC administration of a single dose (6.6 mg/kg) of CCFA. Thus, CCFA might be useful for the treatment of common respiratory tract pathogens in sheep.
Show more [+] Less [-]Comparative pharmacokinetics of levamisole-oxyclozanide combination in sheep and goats following per os administration
2014
Gokbulut, Cengiz | Yalinkilinc, Hande Sultan | Aksit, Dilek | Veneziano, Vincenzo
Since there is no registered anthelmintic drug available for use in goats, extra-label use of drugs is a common practice in most countries. The aim of the present study was to compare the pharmacokinetic disposition of levamisole (LVM)-oxyclozanide (OXZ) combination in sheep and goats following per os administration. Goats (n = 8) and sheep (n = 8) 12- to 16-months-old were used for this study. The animals received tablet formulation of LVM and OXZ combination orally at a dose of 7.5 mg/kg and 15 mg/kg body weight, respectively. Blood samples were collected by jugular vein at different times between 5 min and 120 h after drug administrations. The plasma concentrations of LVM and OXZ were analyzed by HPLC following liquid-liquid phase extraction procedures. The plasma concentrations and systemic availabilities of both LVM and OXZ in goats were lower and the plasma persistence of LVM was shorter compared with those observed in sheep. Terminal half-lives (t1/2λz) of both molecules are shorter in goats compared with those in sheep. Goats treated with LVM-OXZ combination at the recommended dose for sheep may result in a reduced efficacy, because of under-dosing, which may increase the risk of drug resistance in parasites. Increased or repeated dose could be a strategy to provide higher plasma concentration and thus to improve the efficacy against the target parasites in goats compared with sheep. However, some adverse reactions may occur since LVM has relatively very narrow therapeutic index due to its nicotine-like structure and effect.
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