Preliminary Pharmacokinetic Study of Structural Analogs of Benzoic Acid, 2-Chloro-5-(((5,6-Dihydro-2-Methyl-1,4-Oxathiin-3-yl) Carbonyl)Amino)-1-Methylethyl Ester (NSC-D615985) in Mice.

摘要

The study was conducted as a preliminary evaluation to determine the plasma levels and to identify possible metabolites of four structural analogs of NSC-D615985 in mice. Mice were treated with a single IV injection of one of the four drugs formulated in Liposyn II at a dose of 10 mg/kg. Sixteen mice were dosed per group with each group receiving a different analog. Four mice/group were killed and blood samples collected 5, 15, 30, and 60 minutes after dosing. The plasma was separated and analyzed for concentration of each drug. Measured drug concentrations of the four formulated doses varied from 0.284 mg/mL to 0.744 mg/mL verses a target concentration of 1.0 mg/mL. Detectable plasma concentrations of two of the four analogs were measured in mice 5 minutes after treatment, but not at later timepoints; while there was no measurable drug in the plasma of mice treated with the other analogs. These results suggest that either the drugs were rapidly metabolized (within 5 minutes of treatment) or trapped outside of the systemic circulation. Because there were few time points at which plasma drug levels were quantifiable, no pharmacokinetic parameters were calculated.