Background: Emerging antimicrobial resistance prompts evaluation of alternative antimicrobial regimens and drug combinations such as doxycycline and rifampin. Rifampin induces hepatic drug-metabolizing enzymes and could reduce doxycycline concentrations during chronic co-administration.
Objectives: 1) Characterize plasma and pulmonary epithelial lining fluid (PELF) concentrations of doxycycline and rifampin during chronic co-administration in healthy foals; 2) Compare drug concentrations before and after chronic co-administration. Animals: Six university-owned healthy Quarter horse foals.
Methods: Foals received oral doxycycline (10mg/kg) and rifampin (5mg/kg) q12h for 15 days. Plasma was collected at 0.25, 0.5, 1, 2, 4, 6, 12, and 24 hours post doxycycline/rifampin administration on days 0 and 15. PELF was also collected 2 and 12 hours post administration on these days. Total drug concentrations were determined via UPLC-MS/MS. Pharmacokinetic parameters were determined with non-compartmental methods and compared between days 0 and 15 with t-tests and mixed models (p < 0.05).
Results: Plasma doxycycline Cmax was significantly higher on day 15 vs. day 0 (1.48±0.56 vs. 0.82±0.13μg/mL; p = 0.046). Doxycycline PELF concentrations were significantly higher at 2 hours post-dosing on day 15 vs. day 0 (1.57±1.1 vs. 0.57±0.37ug/mL; p = 0.04). Plasma rifampin Cmax was significantly higher on day 15 vs. day 0 (5.63±1.05 vs. 2.97±1.05μg/mL; p = 0.01). Pulmonary rifampin concentrations were comparable among days/times (p > 0.27). Conclusions and Clinical Importance: Co-administration of doxycycline and rifampin for two weeks did not reduce plasma or PELF concentrations of either drug. Nevertheless, doxycycline’s high protein binding impacts efficacy and should be considered during therapeutic decisions.
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