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  • Author or Editor: A. Morrie Craig x
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Objective—To compare hepatic metabolism of pyrrolizidine alkaloids (PAs) between sheep and cattle and elucidate the protective mechanism of sheep.

Sample Population—Liver microsomes and cytosol from 8 sheep and 8 cattle.

Procedure—The PA senecionine, senecionine N-oxide (nontoxic metabolite) and 6,7-dihydro-7-hydroxy- 1-hydroxymethyl-5H-pyrrolizine (DHP; toxic metabolite) were measured in microsomal incubations. The kcat (turnover number) was determined for DHP and N-oxide formation. Chemical and immunochemical inhibitors were used to assess the role of cytochrome P450s, flavin-containing monooxygenases (FMOs), and carboxylesterases in senecionine metabolism. The CYP3A, CYP2B, and FMO concentrations and activities were determined, in addition to the role of glutathione (GSH) in senecionine metabolism.

Results—DHP concentration did not differ between species. Sheep formed more N-oxide, had higher N-oxide kcat, and metabolized senecionine faster than cattle. The P450 concentrations and isoforms had a large influence on DHP formation, whereas FMOs had a large influence on N-oxide formation. In cattle, CYP3A played a larger role in DHP formation than in sheep. FMO activity was greater in sheep than in cattle. Addition of GSH to in vitro microsomal incubations decreased DHP formation; addition of cytosol decreased N-oxide formation.

Conclusions and Clinical Relevance—Hepatic metabolism differences alone do not account for the variation in susceptibility seen between these species. Rather, increased ruminal metabolism in sheep appears to be an important protective mechanism, with hepatic enzymes providing a secondary means to degrade any PAs that are absorbed from the rumen. (Am J Vet Res 2004;65:1563–1572)

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in American Journal of Veterinary Research


Objective—To determine whether iontophoretic administration of dexamethasone to horses results in detectable concentrations in synovial fluid, plasma, and urine.

Animals—6 adult mares.

Procedure—Iontophoresis was used to administer dexamethasone. Treatments (4 mA for 20 minutes) were administered to a tarsocrural joint of each mare. The drug electrode contained 3 ml of dexamethasone sodium phosphate at a concentration of 4 or 10 mg/ml. Samples of synovial fluid, blood, and urine were obtained before and 0.5, 4, 8, and 24 hours after each treatment. All samples were tested for dexamethasone using an ELISA. Synovial fluid also was evaluated for dexamethasone, using high-performance liquid chromatography.

Results—The lower and upper limits of detection for dexamethasone in synovial fluid with the ELISA were 0.21 and 1.5 ng/ml, respectively. Dexamethasone administered at a concentration of 10 mg/ml was detected by the ELISA in synovial fluid of 5 mares from 0.5 to 24 hours and in urine of 4 mares from 0.5 to 8 hours after each treatment, but it was not detected in plasma. Mean synovial fluid concentration of dexamethasone was 1.01 ng/ml. Dexamethasone administered at a concentration of 4 mg/ml was detected by the ELISA in urine of 2 mares at 0.5 and 4 hours after treatment, but it was not detected in synovial fluid or plasma.

Conclusion and Clinical Relevance—Iontophoresis cannot be considered an effective method for delivery of dexamethasone to synovial fluid of horses, because drug concentrations achieved in this study were less than therapeutic concentrations. (Am J Vet Res 2002;63:11–14)

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in American Journal of Veterinary Research


Objective—To determine the serum concentrations and sedative effects of fentanyl after transdermal administration at 3 dosages in llamas.

Animals—9 healthy adult female llamas (mean age, 8 ± 3 years; mean weight, 150 ± 18 kg).

Procedure—Llamas were allocated to 1 of 3 groups (3 llamas/group). Fentanyl patches (each providing transdermal delivery of 75 µg of fentanyl/h) were placed on shaved areas of the antebrachium of all llamas. In group 1, llamas were treated with 1 patch (anticipated fentanyl dosage, 75 µg/h). In group 2, llamas were treated with 2 patches (anticipated fentanyl dosage, 150 µg/h). In group 3, llamas were treated with 4 patches (anticipated fentanyl dosage, 300 µg/h). For each llama, the degree of sedation was assessed by use of a subjective scoring system and a blood sample was collected for determination of serum fentanyl concentration at 12, 24, 36, 48, 60, and 72 hours after patch placement.

Results—Following the placement of 4 patches, mean ± SD serum fentanyl concentration in group 3 llamas reached 0.3 ± 0.08 ng/mL within 12 hours. This concentration was sustained for 72 hours. In group 2, application of 2 patches provided inconsistent results; in group 1, application of 1 patch rarely provided measurable serum fentanyl concentrations. No llamas became sedated at any time.

Conclusions and Clinical Relevance—Results suggest that application of four 75 µg/h fentanyl patches provides consistent, sustained serum fentanyl concentrations without sedation in llamas. However, the serum concentration of fentanyl that provides analgesia in llamas is not known. (Am J Vet Res 2005;66:907–909)

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in American Journal of Veterinary Research
Tending Animals in the Global Village—A Guide to International Veterinary Medicine . . . . Import Risk Analysis: Animals and Animal Products . . . . Exotic Pests & Disease: Biology and Economics for Biosecurity . . . . Borna Disease Virus and Its Role in Neurobehavioral Disease . . . . Foot and Mouth Disease: Facing the New Dilemmas . . . . Trends in Emerging Viral Infections of Swine . . . . Clinical Examination of Farm Animals . . . . Manual of Sheep Diseases (2nd edition) . . . . Mycotoxins: Risks in Plant, Animal, and Human Systems . . . . A Guide to Plant Poisoning of Animals in North America . . . . Diseases of Poultry (11th edition) . . . . Modern Concepts of Immunology in Veterinary Medicine—Poultry Immunology (Advances in Medical and Veterinary Immunology) . . . . Pathology of Pet and Aviary Birds . . . . Birds of Prey: Health and Disease (3rd edition) . . . . Hand-Rearing Wild and Domestic Mammals . . . . Handbook of Wildlife Chemical Immobilization (International Edition) . . . . Veterinary Anesthesia and Pain Management Secrets . . . . The Veterinary ICU Book . . . . Anatomy of the Dog: An Illustrated Text (4th Edition) . . . . The 5-Minute Veterinary Consult Clinical Companion: Small Animal Dermatology . . . . Abdominal Radiology for the Small Animal Practitioner (Made Easy Series) . . . . Two Dimensional and M-Mode Echocardiography for the Small Animal Practitioner (Made Easy Series) . . . . Small Animal Ophthalmology Secrets . . . . Ocular Tumors in Animals and Humans . . . . Feline Oncology: A Comprehensive Guide to Compassionate Care . . . . Veterinary Medicine and Practice 25 Years in the Future and the Economic Steps to Get There
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in Journal of the American Veterinary Medical Association