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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 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.
Show more [+] Less [-]In vivo assessment of a multicomponent and nanostructural polymeric matrix as a delivery system for antimicrobials and bone morphogenetic protein-2 in a unicortical tibial defect in goats
2014
Rousseau, Marjolaine | Anderson, David E. | Lillich, James D. | Apley, Michael D. | Jensen, Peder J. | Biris, Alexandru S.
Objective-To determine the response of cortical bone to a multicomponent and nanostructural polymeric matrix as a drug delivery system for enhancing bone healing. Animals-20 healthy adult crossbred goats. Procedures-A 3.5-mm-diameter unicortical defect was created in each tibia (day 0), and goats (4 goats/group) were treated as follows: not treated (control group), grafted with the matrix, grafted with antimicrobial (tigecycline and tobramycin)-impregnated matrix, grafted with recombinant human bone morphogenetic protein type 2 (rhBMP-2)-impregnated matrix, or grafted with antimicrobial- and rhBMP-2-impregnated matrix. Elution kinetics of antimicrobials was monitored through plasma concentrations. Bone response was assessed with radiographic scoring (days 1 and 30) and dual-energy x-ray absorptiometry (days 1, 14, and 30). Goats were euthanized on day 30, and histomorphologic analysis was performed. Categorical variables were analyzed with a generalized linear model, and continuous variables were analyzed with an ANOVA. Results-Plasma antimicrobial concentrations indicated continued release throughout the study. Radiography and dual-energy x-ray absorptiometry did not reveal significant differences among treatments on day 30. Periosteal reactions were significantly greater surrounding bone defects grafted with rhBMP-2–impregnated matrix than those not treated or grafted with matrix or with antimicrobial-impregnated matrix; periosteal reactions were similar in bone defects grafted with rhBMP-2–impregnated matrix and antimicrobial- and rhBMP-2-impregnated matrix. Conclusions and Clinical Relevance-The matrix served as an antimicrobial delivery system and stimulated bone proliferation when rhBMP-2 was present. Antimicrobial and rhBMP-2 can be used concurrently, but the presence of antimicrobials may affect the performance of rhBMP-2.
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 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 [-]Levamisole resistance to a strongyle population in a smallholder goat farm in Malaysia
2014
Lily Rozita M. H. | Premaalatha, B. | Jamnah O. | Chandrawathani P. | Thongsahuan, S. | Ramlan M. | Erwanas, A. I | Chethanond, U.
The faecal egg count reduction test (FECRT) was conducted on local goats in a smallholder farm on the outskirts of Ipoh. Levamisole drug tested for resistance against strongyles, was administered orally at the rate of 10 mg/kg body weight. Results showed that thestrongyle worm population was resistant to levamisole. The percentage reduction was 75% and lower confidence limit less than 90%. The worm population was made up mainly of Haemonchus contortus(71%), followed by Oesophagostomum sp.(18%) and Trichostrongylus sp. (11%). This finding indicates that anthelmintic resistance is an existing problem in Malaysia, even on a small farm. Alternativeapproaches to chemical anthelmintics have been recommended to controlnematodes in goats such as improved grazing management, herbal medication or biological control, to delay the occurrence of chemical resistance and prevent severe helminth infections in goat flocks.
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