Pharmacokinetic Study of Sudaxine in Dog Plasma Using Novel LC/MS/MS method.

CONTEXT: Sudaxine is a novel respiratory stimulant that increases ventilatory drive via NO+ -thiolate signaling and is under development for reversal of opioid-induced respiratory depression and other critical care indications.

OBJECTIVE: This study investigates the pharmacokinetic characteristics after intravenous administration of Sudaxine by using a simple LC-MS/MS method.

MATERIALS AND METHODS: A sensitive LC-MS/MS method was validated to determine the concentration of Sudaxine in beagle dog plasma after intravenous administration of Sudaxine at (3, 10, 30 and 100 mg/kg). Blood samples (1 ml) were collected at designated time points and SDX concentration was measured for pharmacokinetic study.

RESULTS: The calibration curve was linear within the range of 50-5,000 ng/ml with the lower limit of quantification at 50 ng/ml. The CTmax for all doses was reached at 10 min (Tmax ). Over the dose range studied, average concentration - time curves and systemic exposure (CTmax and AUC0-t ) increased to Sudaxine dose. The terminal half-life of Sudaxine in dogs ranged from 10-30 min and about 17.3±1.0 % of Sudaxine was protein-bound in dog plasma.

DISCUSSION AND CONCLUSIONS: We developed a novel LC-MS/MS method of Sudaxine detection and quantification and determined its pharmacokinetic profiles after intravenous administration in canine subjects. Sudaxine followed first-order kinetics with rapid dose-dependent clearance rates and short half-life making it an ideal candidate for use in critical care setting with intramuscular or IV administration.