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. 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 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. 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.
© 2010 EVJ Ltd.
Publication Date: 2011-05-27 PubMed ID: 21059069DOI: 10.1111/j.2042-3306.2010.00262.xGoogle Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research investigates the optimal time period for feed restriction before administering the drug dantrolene sodium to horses, to prevent negative impacts on its absorption into the bloodstream. The study concluded that feed restriction should not exceed 4 hours prior to oral administration.
Study Objective and Hypothesis
- The objective of this study was to ascertain a minimal duration for feed restriction to optimize plasma dantrolene concentrations in horses after they receive the medication.
- The hypothesis was that feed restriction for either 4, 8, or 12 hours prior to dantrolene administration could result in higher plasma concentrations of the drug, compared to no feed restriction.
Methodology
- Five healthy horses were rotated through four feed restriction periods—0, 4, 8, and 12 hours—before being given dantrolene sodium (6 mg/kg by weight) via a nasogastric tube.
- Plasma concentrations of the drug were measured at various intervals (60, 90, 120, 150, 180, and 210 minutes) post-administration, using a method called spectrofluorometry.
- Collected data was then analyzed using a statistical method known as repeated measures ANOVA.
Research Findings
- Peak plasma levels of dantrolene were observed when horses had undergone feed restriction for 0 and 4 hours, but were lower when horses had been subject to 8 and 12 hours of feed restriction.
- There was no significant difference in mean plasma dantrolene concentration between horses with 0 and 4 hours of feed restriction at any sampled time.
- However, a feed restriction of 8 hours led to a significantly lower plasma dantrolene concentration at 60 and 180 minutes after treatment compared to when horses were restricted for 0 and 4 hours.
- When horses were restricted from feed for 12 hours, plasma dantrolene concentration was significantly lower at all sample times when compared to no restriction or a 4-hour restriction period.
Conclusion
- The results of the study indicated that feed restriction prior to dantrolene administration inhibits the drug’s absorption. Therefore, to achieve optimal plasma dantrolene concentrations, it was recommended that feed restriction should not exceed 4 hours prior to the oral administration of the drug.
Cite This Article
APA
McKenzie EC, Garrett RL, Payton ME, Riehl JH, Firshman AM, Valberg SJ.
(2011).
Effect of feed restriction on plasma dantrolene concentrations in horses.
Equine Vet J Suppl(38), 613-617.
https://doi.org/10.1111/j.2042-3306.2010.00262.x Publication
Researcher Affiliations
- Department of Clinical Sciences, Oregon State University, USA. erica.mckenzie@oregonstate.edu
MeSH Terms
- Animals
- Dantrolene / blood
- Dantrolene / pharmacokinetics
- Female
- Food Deprivation
- Horses / blood
- Male
- Muscle Relaxants, Central / blood
- Muscle Relaxants, Central / pharmacokinetics
- Time Factors
Citations
This article has been cited 1 times.- Fernandez-Fuente M, Terracciano CM, Martin-Duque P, Brown SC, Vassaux G, Piercy RJ. Calcium homeostasis in myogenic differentiation factor 1 (MyoD)-transformed, virally-transduced, skin-derived equine myotubes.. PLoS One 2014;9(8):e105971.
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