Single- and multiple dose pharmacokinetics and multiple dose pharmacodynamics of oral ABT-116 (a TRPV1 antagonist) in dogs.
Six dogs were used to determine single and multiple oral dose pharmacokinetics of ABT-116. Blood was collected for subsequent analysis prior to and at 15, 30 min and 1, 2, 4, 6, 12, 18, and 24 h after administration of a single 30 mg/kg dose of ABT-116. Results showed a half-life of 6.9 h, k(el) of 0.1/h, AUC of 56.5 μg·h/mL, T(max) of 3.7 h, and C(max) of 3.8 μg/mL. Based on data from this initial phase, a dose of 10 mg/kg of ABT-116 (no placebo control) was selected and administered to the same six dogs once daily for five consecutive days. Behavioral observations, heart rate, respiratory rate, temperature, thermal and mechanical (proximal and distal limb) nociceptive thresholds, and blood collection were performed prior to and 4, 8, and 16 h after drug administration each day. The majority of plasma concentrations were above the efficacious concentration (0.23 μg/mL previously determined for rodents) for analgesia during the 24-h sampling period. Thermal and distal limb mechanical thresholds were increased at 4 and 8 h, and at 4, 8, and 16 h respectively, postdosing. Body temperature increased on the first day of dosing. Results suggest adequate exposure and antinociceptive effects of 10 mg/kg ABT-116 following oral delivery in dogs.
Department of Clinical Sciences, College of Veterinary Medicine and Biomedical sciences, Colorado State University, Fort Collins, CO, USA.|Department of Companion Animal Clinical Sciences, Faculty of Veterinary Medicine, Kasetsart University, Bangkok, Thailand.
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Niyom
Department of Clinical Sciences, College of Veterinary Medicine and Biomedical sciences, Colorado State University, Fort Collins, CO, USA.
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Mama
Department of Clinical Sciences, College of Veterinary Medicine and Biomedical sciences, Colorado State University, Fort Collins, CO, USA.
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Gustafson
Department of Clinical Sciences, College of Veterinary Medicine and Biomedical sciences, Colorado State University, Fort Collins, CO, USA.
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D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D002853:Chromatography, Liquid; D004285:Dogs / Q000097:blood*; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D007191:Indazoles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008954:Models, Biological; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*; D053719:Tandem Mass Spectrometry
C551310:ABT 116; D007191:Indazoles; D010671:Phenylurea Compounds; D050916:TRPV Cation Channels