| Simultaneous and minimally invasive assessment of muscle tolerance and bioavailability of different volumes of an intramuscular formulation in the same animals. | |
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MedLine Citation:
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PMID: 16612034 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Evaluation of skeletal muscle tolerance during development of new drug formulations for i.m. use is most often based on terminal methods performed in the target species after slaughtering. The objective of this study was to evaluate the effect of muscle damage on the pharmacokinetic parameters of the drug delivered into the muscle using an alternative, noninvasive method. Phenylbutazone (PBZ) was used as the test article. Six ewes received increasing volumes of a 20% PBZ i.m. formulation, according to a cross-over design, and an i.v. bolus of the same formulation. Serial blood samples were taken, and a pharmacokinetic analysis of the plasma activity of creatine kinase and plasma PBZ concentrations was carried out. The amount of muscle damage after i.m. administration of 2, 4, or 8 mL of PBZ, calculated from the area under the curve of plasma creatine kinase across time was 36, 76, and 178 g for a 70-kg ewe. The corresponding absolute bioavailability of PBZ was 100 +/- 32%, 96 +/- 19%, and 100 +/- 17%, and the maximal PBZ concentrations were 42 +/- 3.4, 74 +/- 8.8, and 119 +/- 18.2 microg/mL. The plasma clearance of PBZ (i.v.) was 4.2 +/- 0.94 mL.kg(-1).h(-1). In conclusion, the absolute bioavailability of PBZ after i.m. administration was not altered by the increased volume of formulation administered despite the overall increase in the extent of muscle damage. |
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Authors:
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P J Ferre; V Laroute; J P Braun; J Cazaux; P L Toutain; H P Lefebvre |
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Publication Detail:
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Type: Clinical Trial; Journal Article |
Journal Detail:
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Title: Journal of animal science Volume: 84 ISSN: 1525-3163 ISO Abbreviation: J. Anim. Sci. Publication Date: 2006 May |
Date Detail:
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Created Date: 2006-04-13 Completed Date: 2006-10-19 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8003002 Medline TA: J Anim Sci Country: United States |
Other Details:
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Languages: eng Pagination: 1295-301 Citation Subset: IM |
Affiliation:
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Unité Mixte de Recherche 181 INRA/ENVT, Experimental Pathophysiology and Toxicology, National Veterinary School of Toulouse, 23 Chemin des Capelles, BP 87614, 31076 Toulouse cedex 03, France. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*, adverse effects*, pharmacokinetics Biological Availability Chemistry, Pharmaceutical Creatine Kinase / blood Cross-Over Studies Dose-Response Relationship, Drug Female Half-Life Injections, Intramuscular Muscle, Skeletal Phenylbutazone / administration & dosage*, adverse effects*, pharmacokinetics Random Allocation Sheep* |
| Chemical | |
Reg. No./Substance:
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0/Anti-Inflammatory Agents, Non-Steroidal; 50-33-9/Phenylbutazone; EC 2.7.3.2/Creatine Kinase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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