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

BACKGROUND: The effect of food on minocycline oral absorption in dogs is unknown. OBJECTIVE: The objective was to determine the pharmacokinetics of minocycline after administration of a single oral dose in fed and fasted dogs. METHODS: Ten 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. RESULTS: No significant difference was found between treatments for AUC (P = 0.0645), although AUC was higher in fasted dogs. A significant difference was found for CMAX (P = 0.0059), with fasted dogs attaining a higher CMAX . The covariate of fed versus fasted accounted for a significant variation in the pharmacokinetics. CONCLUSIONS AND CLINICAL IMPORTANCE: Because 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.

Evaluation of canine-specific minocycline and doxycycline susceptibility breakpoints for meticillin-resistant Staphylococcus pseudintermedius isolates from dogs.

BACKGROUND: Using the US Clinical and Laboratory Standards Institute (CLSI) human tetracycline breakpoints to predict minocycline and doxycycline susceptibility of Staphylococcus pseudintermedius (SP) isolates from dogs is not appropriate because they are too high to meet pharmacokinetic/pharmacodynamic data using a standard dose. New breakpoints have been approved for doxycycline and proposed for minocycline. Revised breakpoints are four dilutions lower than tetracycline breakpoints, providing a more conservative standard for classification of isolates. HYPOTHESIS/OBJECTIVES: The objectives of this study were to measure minimum inhibitory concentrations (MICs) of minocycline and doxycycline of 100 canine meticillin-resistant SP clinical isolates, compare their susceptibilities to minocycline and doxycycline based on current and revised standards, and document their tetracycline resistance genes. METHODS: E-test strips were used to determine MICs. PCR was used to identify tet genes. RESULTS: Using the human tetracycline breakpoint of MIC ≤ 4 µg/mL, 76 isolates were susceptible to minocycline and 36 isolates were susceptible to doxycycline. In contrast, using the proposed minocycline breakpoint (MIC ≤ 0.25 µg/mL) and approved doxycycline breakpoint (MIC ≤ 0.125 µg/mL), 31 isolates were susceptible to both minocycline and doxycycline. Thirty-one isolates carried no tet genes, two had tet(K) and 67 had tet(M). CONCLUSIONS AND CLINICAL IMPORTANCE: Use of the human tetracycline breakpoints misclassified 45 and five of the isolates as susceptible to minocycline and doxycycline, respectively. PCR analysis revealed that 43 and five of the isolates classified as susceptible to minocycline and doxycycline, respectively, possessed the tetracycline resistance gene, tet(M), known to confer resistance to both drugs. These results underscore the importance of utilizing the proposed minocycline and approved doxycycline canine breakpoints in place of human tetracycline breakpoints.