PK/PD analysis of trazodone and gabapentin in neuropathic pain rodent models: Translational PK-PD modeling from nonclinical to clinical development.

ABSTRACT: A pharmacokinetic/pharmacodynamic (PK/PD) model was developed to describe the time course of writhings after intraperitoneal injection of acetic acid in mice. The model was applied to investigate the antinociceptive effect of trazodone and gabapentin alone and in combination. Writhings time course was described by a transit compartment model with the delay due to the transit of the acetic acid being represented by a chain of intermediate compartments. In the drug-treated animals, the number of writhings decreases according to a k₂ factor linking drug concentration and antinociceptive effect. Compounds' potency parameters were 10.9 and 0.0459 L/μmoles/min for trazodone and gabapentin, respectively, indicating a much higher in vivo potency of trazodone in the PD writhing test. The

SUBMITTER: Oggianu L 

PROVIDER: S-EPMC10087074 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature