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 2 h (MS+2) on minocycline pharmacokinetics, and established dosing recommendations based on pharmacodynamic indices. Oral minocycline (300 mg) and sucralfate suspension (1 g) 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 1.15 μg/mL and 8.0 h* μg/mL, respectively. The CMAX and AUC were significantly lower (P< 0.05) in the MS group (CMAX = 0.33 μg/mL, AUC 3.0 h*μg/mL) compared with M or MS+2 (CMAX = 0.97 μg/mL, AUC 10.3 h*μg/mL). Delaying sucralfate by 2 h did not decrease oral minocycline absorption, but concurrent administration significantly decreased minocycline absorption. A dose of 7.5 mg/kg p.o. q12 h achieves the pharmacodynamic index for a bacterial minimum inhibitory concentration (MIC) of 0.25 μg/mL (AUC:MIC≥33.9).

The effect of sucralfate tablets vs. suspension on oral doxycycline absorption in dogs

“…This theory was supported by finding significant decreases in both AUC and C MAX when doxycycline was administered concurrently with sucralfate suspension, with only 20% relative bioavailability as compared with doxycycline alone. This documented interaction between concurrently administered doxycycline and sucralfate suspension in dogs is consistent with results of a study documenting an interaction between doxycycline and aluminum hydroxide in 10 human volunteers (Deppermann et al ., ) as well as consistent with the documented interaction between concurrent minocycline and sucralfate suspension in dogs (KuKanich et al ., ). Based on the differences documented in T MAX , administration of sucralfate suspension concurrently with doxycycline appeared to decrease the rate of absorption of doxycycline; however, this effect was minor and unlikely to be clinically relevant.…”

“…Extrapolating from this information, veterinary formularies recommend administration of oral tetracyclines and fluoroquinolones at least 2 h before or after sucralfate (Plumb, ,b) or at least 30 min before administering sucralfate (Papich, ). A recent study documented an interaction when minocycline and sucralfate suspension were administered concurrently to dogs, with the relative bioavailability of concurrent administration being 35% as compared with minocycline administered alone (KuKanich et al ., ). In that study, delaying sucralfate by 2 h was sufficient to avoid this interaction and allow optimal absorption of minocycline (KuKanich et al ., ).…”

“…A recent study documented an interaction when minocycline and sucralfate suspension were administered concurrently to dogs, with the relative bioavailability of concurrent administration being 35% as compared with minocycline administered alone (KuKanich et al ., ). In that study, delaying sucralfate by 2 h was sufficient to avoid this interaction and allow optimal absorption of minocycline (KuKanich et al ., ). However, studies to confirm reduced bioavailability when sucralfate is administered with doxycycline to dogs have not been performed to date; therefore, these extrapolations may not be accurate for doxycycline.…”

Effect of Sucralfate on the Relative Bioavailability of Enrofloxacin and Ciprofloxacin in Healthy Fed Dogs

“…Current veterinary formularies cite a potential interaction between sucralfate and both fluoroquinolone and tetracycline antimicrobials, caused by binding of the aluminum component of sucralfate with the antimicrobial, resulting in non‐absorbable chelate complexes and decreased bioavailability of the antimicrobial . Interactions between sucralfate and both doxycycline and minocycline have been verified in dogs; however, research to validate an interaction of sucralfate with fluoroquinolones in dogs has not been reported.…”

Efficacy of Minocycline in Naturally Occurring Nonacute Ehrlichia canis Infection in Dogs

“…Minocycline, another drug in the tetracycline family, has been used as an alternative to doxycycline in veterinary medical practices, with pharmacokinetic studies performed for some dieases . Little information is available regarding efficacy of minocycline for the treatment of rickettsial disease .…”