Effect of feeding on the pharmacokinetics of oral minocycline in healthy research dogs

Veterinary Dermatology - Tập 26 Số 6 - Trang 399 - 2015
Melanie Hnot1, Lynette K. Cole1, Gwendolen Lorch1, Päivi J. Rajala‐Schultz2, Mark G. Papich3
1Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, 601 Vernon L. Tharp. St., Columbus, OH 43210, USA
2Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, 601 Vernon L. Tharp St., Columbus, OH, 43210 USA
3Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, NC 27607, USA

Tóm tắt

BackgroundThe effect of food on minocycline oral absorption in dogs is unknown.ObjectiveThe objective was to determine the pharmacokinetics of minocycline after administration of a single oral dose in fed and fasted dogs.MethodsTen research hounds were administered oral minocycline (approximately 5 mg/kg) with and without food, in a crossover study, with a one‐week wash‐out between treatments. Blood samples were collected immediately prior to minocycline administration and over 24 h. Minocycline plasma drug concentrations were measured using high‐performance liquid chromatography using ultraviolet detection and were analysed with compartmental modelling to determine primary pharmacokinetic parameters. Each dog was analysed independently, followed by calculation of means and variation of the dogs. The Wilcoxon signed–rank test [analysing secondary pharmacokinetic parameters – peak concentration (CMAX), area under the concentration versus time curve (AUC)] was used to compare the two groups. A population pharmacokinetic modelling approach was performed using nonlinear mixed effects modelling of primary parameters for the population as fixed effects and the difference between subjects as a random effect. Covariate analysis was used to identify the source of variability in the population.ResultsNo significant difference was found between treatments forAUC(P = 0.0645), althoughAUCwas higher in fasted dogs. A significant difference was found forCMAX(P = 0.0059), with fasted dogs attaining a higherCMAX. The covariate of fed versus fasted accounted for a significant variation in the pharmacokinetics.Conclusions and clinical importanceBecause feeding was a significant source of variation for the population's primary pharmacokinetic parameters and fasted dogs had higher minocycline concentrations, we recommend administering minocycline without food.

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Veterinary Dermatology

Tập 26 Số 6

399

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