Population Pharmacokinetic-Pharmacodynamic Analysis of a Reserpine-Induced Myalgia Model in Rats.

(1) Background: Fibromyalgia syndrome (FMS) is a chronic pain condition with widespread pain and multiple comorbidities, for which conventional therapies offer limited benefits. The reserpine-induced myalgia (RIM) model is an efficient animal model of FMS in rodents. This study aimed to develop a pharmacokinetic-pharmacodynamic (PK-PD) model of reserpine in rats, linking to its impact on monoamines (MAs). (2) Methods: Reserpine was administered daily for three consecutive days at dose levels of 0.1, 0.5, and 1 mg/kg. A total of 120 rats were included, and 120 PK and 828 PD observations were collected from 48 to 96 h after the first dose of reserpine. Non-linear mixed-effect data analysis was applied for structural PK-PD model definition, variability characterization, and covariate analysis. (3) Results: A one-compartment model best described reserpine in rats (V = 1.3 mL/kg and CL = 4.5 × 10