To determine the time-course of plasma and CSF concentrations of intravenous (IV) ondansetron in healthy subjects, with and without selective inhibition of Pgp efflux transporter.
The study hypothesis is that inhibition of Pgp efflux transporters will increase the CNS bio-distribution of the 5-HT3R antagonist ondansetron. Specifically: 1. Intravenous administration of ondansetron is expected to yield low CSF exposure. 2. Co-administration of ondansetron with intravenous tariquidar, an inhibitor of Pgp efflux transporters, will result in increased CSF exposure of ondansetron.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
SINGLE
Enrollment
14
Each participant will receive two IV infusions of ondansetron, 24 hours apart. In the first and second sessions, respectively, placebo (D5W) or tariquidar (4mg/kg dose in D5W) 22 will be administered IV over 60 minutes. Ondansetron will be diluted in 50mL 0.9% normal saline, and tariquidar will be diluted in 250mL D5W.
Each participant will receive two IV infusions of ondansetron, 24 hours apart. In the first and second sessions, respectively, placebo (D5W) or tariquidar (4mg/kg dose in D5W) 22 will be administered IV over 60 minutes. Ondansetron will be diluted in 50mL 0.9% normal saline, and tariquidar will be diluted in 250mL D5W.
Washington University in St. Louis
St Louis, Missouri, United States
CSF penetration of ondansetron with and without tariquidar - area under the curve (AUC)
CSF penetration of intravenous ondansetron will be determined as AUCCSF0-∞ of ondansetron, and compared between the two sessions, with and without tariquidar
Time frame: 48 hours
Cmax CSF
Maximum CSF concentration (Cmax CSF) of ondansetron, compared between the sessions
Time frame: 48 hours
CSF:plasma concentration ratio
CSF:plasma concentration ratio of ondansetron, compared between the two sessions
Time frame: 48 hours
Plasma Cmax
Maximum plasma concentration (Cmax) of ondansetron, compared between the sessions
Time frame: 48 hours
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