Abstract: Background - NMXSS75A®, a novel S-adenosylmethionine (SAMe), is marketed for equine liver disease. The pharmacokinetics and bioavailability have not been published.
Hypothesis/Objectives - The oral SAMe formulation, NMXSS75A®, was hypothesized to reach 1000 ng/ml in plasma using the manufacturer’s dosing regimen.
Animals - Six healthy university-owned adult horses, 3-20 years old, mixed breeds, 3 mares and 3 geldings, with no biochemical evidence of liver disease.
Methods - A randomized crossover pharmacokinetic study was performed. Each horse received their daily feed ration and oral SAMe (NMXSS75A®, 20 mg/kg PO) per the product label, and SAMe tosylate (0.5 mg SAMe/kg IV as a 10-minute infusion), with a two-week washout period between treatments. Plasma SAMe concentrations were measured serially for 48 hours using liquid chromatography tandem mass spectrometry.
Results - Pharmacokinetic parameters after IV infusion were maximum plasma concentration (Cmax) 3444 ng/ml (2474-4343), time to peak plasma concentration (Tmax) 7 minutes (0.12 hours; 0.03-0.16), and terminal elimination half-life (T½) 1.1 hours (range 0.49-2.99). Pharmacokinetic parameters after PO administration were Cmax 656 ng/ml (371-812), Tmax 30 minutes (same for all horses), and T½ 1.1 hours (range 0.49-2.99). The mean bioavailability of NMXSS75A® was 1.2% (range 1-2%).
Conclusions and Clinical Importance - The Cmax and bioavailability of NMXSS75A® were lower than anticipated in fed horses and should be compared to administration in fasted horses and to other oral formulations of SAMe. While Cmax is lower than recommended for other conditions, therapeutic efficacy for liver conditions is unknown and further studies are warranted.
