Effect of feed restriction on plasma dantrolene concentrations in horses

P>Reasons for performing study: Dantrolene sodium is used to prevent exertional rhabdomyolysis in predisposed horses. Food intake might negatively impact dantrolene bioavailability in horses; however, prolonged feed restriction might be detrimental to performance. Objective: To determine a minimum duration of feed restriction that would optimise plasma dantrolene concentrations in horses after nasogastric administration. It was hypothesised that feed restriction for 4, 8 or 12 h before dantrolene administration would result in higher plasma dantrolene concentrations than achieved with no feed restriction before treatment. Methods: Five healthy horses were randomly rotated through 4 feed restriction periods of 0, 4, 8 and 12 h duration prior to nasogastric administration of dantrolene sodium (6 mg/kg bwt). Plasma dantrolene concentration was measured by spectrofluorometry at 60, 90, 120, 150, 180 and 210 min after administration. Data were analysed via repeated measures ANOVA. Results: Peak plasma dantrolene concentration was highest when horses had 0 and 4 h of feed restriction (0.65 +/- 0.10 mu g/ml at 120 min; 0.66 +/- 0.17 at 180 min, respectively) and was lower when horses were restricted from feed for 8 h (0.45 +/- 0.15 at 150 min) and 12 h (0.21 +/- 0.09 at 180 min). Mean plasma dantrolene concentration did not differ between 0 and 4 h feed restriction at any sample time, but feed restriction for 8 h resulted in significantly lower plasma dantrolene concentration at 60 and 180 min after treatment than when horses were restricted 0 and 4 h, respectively. Plasma dantrolene concentration was significantly lower at all sample times when horses were restricted from feed 12 h compared to 0 or 4 h. Conclusions: Absorption of nasogastrically administered dantrolene is inhibited by feed restriction before administration. To achieve optimal plasma dantrolene concentrations, feed restriction before oral administration should not exceed 4 h.