Pharmacokinetics of doxycycline after oral administration of multiple doses in dogs

• Published in: Journal of veterinary pharmacology and therapeutics Vol. 44; no. 3; pp. 326 - 332
• Main Authors: De Lucas, Jose Julio, Rodríguez, Casilda, San Andrés, Maria Dolores, Sainz, Angel, Villaescusa, Alejandra, García‐Sancho, Mercedes, Rodríguez‐Franco, Fernando, San Andrés, Manuel I.
• Format: Journal Article
• Language: English
• Published: England 01.05.2021
• Subjects: dogs; doxycycline; Monte Carlo; multiple doses; pharmacokinetic‐pharmacodynamics; dogs; pharmacokinetic-pharmacodynamics; Monte Carlo; doxycycline; multiple doses
• ISSN: 0140-7783; 1365-2885
• DOI: 10.1111/jvp.12926

The aim of this study was to determine the pharmacokinetic parameters of doxycycline in dogs and assess the efficacy of an oral drug dosage regimen of 10 mg/kg daily for 28 days through Pharmacokinetic/Pharmacodynamic (PK/PD) target analysis based on Monte Carlo simulation, using previously published data for the zoonotic pathogen Staphylococcus pseudintermedius. After a multiple‐dosage regimen, the accumulation index was 1.88 ± 0.82. The Cmaxss and Cminss values were 5.18 ± 1.81 µg/ml and 1.91 ± 1.35 µg/ml, respectively. There were statistically significant differences for Cmax, Cmin at 24 hr, MRTt, AUCt and AUC∞ between days 1 and 28. The Cminss value was over the MIC of the principal pathogens, and Cmaxss was higher than the resistance values (>2 μg/ml). For AUC/MIC indices of 12, 25 and 40, the cumulative fraction responses (CFR) were 94.01%, 69.55% and 60.86%, respectively; for an MIC value of 2 µg/ml, the corresponding probability of target attainment (PTA) was 99.94%, 84.78% and 45.16%, respectively. Doxycycline was used against numerous localized infections in different organs and tissues. For the strains with MIC < 1 μg/mL, PTA was close to 100%, even for the most demanding ones, specifically 94.98% for an index of 40% and 99.9% for an index of 25.