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Effect of food on the pharmacokinetics of minocycline in healthy research dogs and minocycline and doxycycline susceptibilities of methicillin-resistant Staphylococcus pseudintermedius isolates using current and revised breakpoints

Hnot, Melanie
http://rave.ohiolink.edu/etdc/view?acc_num=osu1429779369

Abstract Details

2015, Master of Science, Ohio State University, Comparative and Veterinary Medicine.
Staphylococcus pseudintermedius (SP) is the most common pathogen isolated from canine superficial pyoderma. Methicillin-resistant S. pseudintermedius (MRSP) is isolated with increasing frequency from these lesions.1 Doxycycline is the member of the tetracyclines that has been most commonly used to treat MRSP infections in dogs,2 while the use of minocycline has only been sporadically reported.3 Clinical and Laboratory Standards Institute (CLSI) human tetracycline breakpoints to predict minocycline and doxycycline susceptibility of SP isolates from dogs are not appropriate because they do not meet pharmacokinetic/pharmacodynamic data using a standard dose. New breakpoints have been approved for doxycycline and proposed for minocycline and are four dilutions lower than tetracycline breakpoints, providing a more conservative standard for classification of isolates. The objectives of this study were to measure MICs of minocycline and doxycycline of 100 canine MRSP clinical isolates, compare their susceptibilities to minocycline and doxycycline based on current and revised standards, and document their tetracycline resistance genes. MICs were determined with E-test strips. PCR was used to identify tet genes. Using the human-derived 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). Use of human-derived tetracycline breakpoints for doxycycline and minocycline susceptibility testing misclassified 45 of 76 (59%) canine MRSP isolates susceptible to minocycline and 5 of 36 (14%) susceptible to doxycycline demonstrating the importance of using the proposed minocycline and approved doxycycline canine specific breakpoints. Minocycline could serve as a reliable alternative to doxycycline for treating dogs with infections caused by SP. Many pet owners prefer to administer oral medications with food; however, this may alter absorption. Since the pharmacokinetics of minocycline in unfed dogs has not been evaluated, the objective of this study was to determine the pharmacokinetics of minocycline after administration of a single oral dose in dogs with and without food. Ten research hounds were administered oral minocycline (approximately 5 mg/kg) with and without food, in a crossover study, with a one-week washout between treatments. Blood samples were collected immediately prior to minocycline administration and over 24 hours. Minocycline plasma drug concentrations were measured using high-performance liquid chromatography and were analyzed to determine primary pharmacokinetic parameters. Wilcoxon signed-rank test was used to compare the two groups. A population pharmacokinetic modeling approach using nonlinear mixed effects modeling for primary parameters for the population as fixed effects and the difference between subjects as a random effect was performed. Covariate analysis was used to identify the source of variability in the population. 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. As the covariate of feeding versus fasted accounted for a significant variation in the pharmacokinetics we recommend administration of minocycline without food.
Lynette Cole (Advisor)
Gwendolen Lorch (Committee Member)
Sandra Diaz (Committee Member)
Joshua Daniels (Committee Member)
Paivi Rajala-Schultz (Committee Member)
166 p.
Veterinary Services

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Citations

  • Hnot, M. (2015). Effect of food on the pharmacokinetics of minocycline in healthy research dogs and minocycline and doxycycline susceptibilities of methicillin-resistant Staphylococcus pseudintermedius isolates using current and revised breakpoints [Master's thesis, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1429779369

    APA Style (7th edition)

  • Hnot, Melanie. Effect of food on the pharmacokinetics of minocycline in healthy research dogs and minocycline and doxycycline susceptibilities of methicillin-resistant Staphylococcus pseudintermedius isolates using current and revised breakpoints. 2015. Ohio State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1429779369.

    MLA Style (8th edition)

  • Hnot, Melanie. "Effect of food on the pharmacokinetics of minocycline in healthy research dogs and minocycline and doxycycline susceptibilities of methicillin-resistant Staphylococcus pseudintermedius isolates using current and revised breakpoints." Master's thesis, Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1429779369

    Chicago Manual of Style (17th edition)

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