Effect of feed restriction on plasma dantrolene concentrations in horses

Abstract

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. 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. 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. Peak plasma dantrolene concentration was highest when horses had 0 and 4 h of feed restriction (0.65 ± 0.10 µg/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. 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.