Effect of sucralfate on oral minocycline absorption in healthy dogs

Abstract

Sucralfate and minocycline may be administered concurrently to dogs. The relative bioavailability of tetracyclines may be reduced if administered with sucralfate, but studies confirming these interactions in dogs are not available. This study evaluated the pharmacokinetics of oral minocycline in dogs (M), determined the effects of concurrent administration of sucralfate and minocycline (MS) on minocycline pharmacokinetics, determined the effects of delaying sucralfate administration by 2h (MS+2) on minocycline pharmacokinetics, and established dosing recommendations based on pharmacodynamic indices. Oral minocycline (300mg) and sucralfate suspension (1g) were administered to five greyhounds in a randomized crossover design. Minocycline plasma concentrations were evaluated using liquid chromatography with mass spectrometry. The maximum plasma concentration (CMAX ) and area under the curve (AUC) of minocycline were 1.15μg/mL and 8.0h* μg/mL, respectively. The CMAX and AUC were significantly lower (P<0.05) in the MS group (CMAX =0.33μg/mL, AUC 3.0h*μg/mL) compared with M or MS+2 (CMAX = 0.97μg/mL, AUC 10.3h*μg/mL). Delaying sucralfate by 2h did not decrease oral minocycline absorption, but concurrent administration significantly decreased minocycline absorption. A dose of 7.5mg/kg p.o. q12h achieves the pharmacodynamic index for a bacterial minimum inhibitory concentration (MIC) of 0.25μg/mL (AUC:MIC≥33.9).