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Pharmacokinetic study of Sudaxine in dog plasma using novel LC–MS/MS method
Author(s) -
Altawallbeh Ghaith,
Smith Laura,
Lewis Stephen J.,
Authier Simon,
Bujold Kim,
Gaston Benjamin,
Bederman Ilya
Publication year - 2019
Publication title -
drug testing and analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 54
eISSN - 1942-7611
pISSN - 1942-7603
DOI - 10.1002/dta.2507
Subject(s) - pharmacokinetics , beagle , context (archaeology) , pharmacology , chromatography , half life , chemistry , medicine , paleontology , biology
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 liquid chromatography–tandem mass spectrometry (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 C Tmax for all doses was reached at 10 minutes (T max ). Over the dose range studied, average concentration – time curves and systemic exposure (C Tmax and AUC 0–t ) increased to Sudaxine dose. The terminal half‐life of Sudaxine in dogs ranged from 10 to 30 minutes 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 a critical care setting with intramuscular or IV administration.