The purpose of this study was to evaluate the pharmacokinetics of the active metabolite of dipyrone, 4-methylaminoantipyrine (4‑MAA), in adult horses following intravenous administration of four different dosing regimens.
Dipyrone was administered intravenously (IV) to 20 healthy adult horses for nine days in a parallel design laboratory study. Horses were randomly assigned to receive 30 mg/kg q12h (n=6), 30 mg/kg q8h (n=4), 60 mg/kg q8h (n=6) or 90 mg/kg q12h (n=6). Blood was collected at predetermined times after administration and plasma 4-MAA concentrations were measured using a high performance liquid chromatography/tandem mass spectrometry (LC/MS/MS) method validated for use in horses.
4-MAA was rapidly detected in the plasma, reaching maximum measured concentrations (C max) at the first time point for all doses studied. Following the first dose, the C max increased linearly over the range of 30-90mg/kg (R2 = 0.884). Following multiple doses, significant accumulation occurred and the area under curve (AUC) increased disproportionate to dose for 60 and 90 mg/kg. Significant differences including increases in minimum concentration (5.89μg/mL vs 2.47 μg/mL), average concentration (15.61 μg/mL vs 8.93 μg/mL), and half-life (11.37 h vs 4.48 h) were noted when dipyrone was administered 30 mg/kg q8h compared to q12h (P < 0.001). No significant differences were noted in clearance or AUC tau.
Higher doses or shorter dosing intervals result in nonlinear pharmacokinetics for 4-MAA following multiple doses. This may be a result of drug accumulation at the dosing regimens utilized in this study, or may represent alterations in metabolism.
Associate Professor of Clinical Pharmacology
VA-MD College of Veterinary Medicine
Dr. Davis received her Bachelor of Science degree in Animal Science and her Doctor of Veterinary Medicine from Virginia Tech. She then did an internship at Mississippi State University in Equine Medicine and Surgery. From there, she completed a residency in Equine Internal Medicine at North Carolina State University, during which time she received a Master’s degree in Specialized Veterinary Medicine and achieved board certification as a specialist in Large Animal Internal Medicine. Following this, she completed a PhD program and residency in Clinical Pharmacology. She also received board certification as a specialist in Veterinary Clinical Pharmacology. Dr. Davis spent 10 years as faculty at North Carolina State University’s College of Veterinary Medicine in Equine Internal Medicine and Clinical Pharmacology. She has recently moved backed to Blacksburg and is currently an Associate Professor of Clinical Pharmacology at the VMCVM. Her research area of interest involves pharmacokinetics/pharmacodynamics of therapeutic and investigational drugs, drug release from novel pharmaceutical forms, and drug stability/strength in compounded formulations.
Friday, June 15
4:45 PM – 5:00 PM
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