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

Abstract

BackgroundSucralfate impairs absorption of ciprofloxacin and other fluoroquinolones in humans, but no sucralfate–fluoroquinolone interaction has been reported in dogs. Veterinary formularies recommend avoiding concurrent administration of these medications, which might impact compliance, therapeutic success, and resistance selection from fluoroquinolones.ObjectivesTo determine whether a drug interaction exists when sucralfate is administered to fed dogs concurrently with ciprofloxacin or enrofloxacin, and whether a 2 hour delay between fluoroquinolone and sucralfate affects fluoroquinolone absorption.AnimalsFive healthy Greyhounds housed in a research colony.MethodsThis was a randomized crossover study. Treatments included oral ciprofloxacin (C) or oral enrofloxacin (E) alone, each fluoroquinolone concurrently with an oral suspension of sucralfate (CS, ES), and sucralfate suspension 2 hours after each fluoroquinolone (C2S, E2S). Fluoroquinolone concentrations were evaluated using liquid chromatography with mass spectrometry.ResultsDrug exposure of ciprofloxacin was highly variable (AUC 5.52–22.47 h μg/mL) compared to enrofloxacin (AUC 3.86–7.50 h μg/mL). The mean relative bioavailability for ciprofloxacin and concurrent sucralfate was 48% (range 8–143%) compared to ciprofloxacin alone. Relative bioavailability of ciprofloxacin improved to 87% (range 37–333%) when sucralfate was delayed by 2 hours. By contrast, relative bioavailability for enrofloxacin and concurrent sucralfate was 104% (94–115%).Conclusions and Clinical ImportanceA possible clinically relevant drug interaction for the relative bioavailability of ciprofloxacin with sucralfate was found. No significant difference in bioavailability was documented for enrofloxacin with sucralfate. Further research is warranted in fasted dogs and clinical cases requiring enrofloxacin or other approved fluoroquinolones in combination with sucralfate.

Gastroprotectants in small animal veterinary practice – a review of the evidence. Part 1: cyto‐protective drugs

“…For example, while bioavailability of enrofloxacin was unchanged by concomitant or delayed administration of sucralfate, ciprofloxacin bioavailability was decreased to 48% when sucralfate suspension was given concomitantly and was 87% when sucralfate suspension was given 2 hours after ciprofloxacin, compared with dogs receiving ciprofloxacin alone (KuKanich et al . ). The absorption of other drugs can also be affected by sucralfate.…”

“…, KuKanich et al . , , KuKanich & KuKanich , Quimby & Lappin ). There were three studies on cats (Clark et al .…”

“…The lowest risk of bias was achieved by three similar studies from the same author, assessing the effect of sucralfate on drug absorption (KuKanich et al . , , KuKanich & KuKanich ). A common cause of bias was the use of purpose‐bred research animals rather than client‐owned animals, meaning that the study group was poorly representative of the general population (Ritschel et al .…”

“…Drug interactions, with reduction of the bioavailability of different antibiotics, antiarrhythmics or meperidine, were clearly observed with sucralfate or aluminium hydroxide with concerns regarding reduction of the efficacy of the drugs given concomitantly with these gastroprotectants (KuKanich et al . , , KuKanich & KuKanich ). Aluminium absorption with potential for aluminium toxicity was observed with both aluminium hydroxide and sucralfate (when co‐administered with cimetidine) (Ritschel et al .…”

“…The effect of sucralfate administration on drug bioavailability is variable between different drugs and the effects on absorption of a specific antibiotic cannot be reliably extrapolated to other antibiotics, even those belonging to the same class. For example, while bioavailability of enrofloxacin was unchanged by concomitant or delayed administration of sucralfate, ciprofloxacin bioavailability was decreased to 48% when sucralfate suspension was given concomitantly and was 87% when sucralfate suspension was given 2 hours after ciprofloxacin, compared with dogs receiving ciprofloxacin alone (KuKanich et al 2016). The absorption of other drugs can also be affected by sucralfate.…”