{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Alfosea-Cuadrado GM"],"funding":["Generalitat Valenciana"],"pagination":["1101"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11359992"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["16(8)"],"pubmed_abstract":["(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<sup>-1</sup> mL/h/kg). A precursor-pool PK-PD model (k<sub>in</sub> = 6.1 × 10<sup>-3</sup> mg/h, k<sub>p</sub> = 8.6 × 10<sup>-4</sup> h<sup>-1</sup> and k<sub>out</sub> = 2.7 × 10<sup>-2</sup> h<sup>-1</sup>) with a parallel transit chain (k<sub>0</sub> = 1.9 × 10<sup>-1</sup> h<sup>-1</sup>) characterized the longitudinal levels of MA in the prefrontal cortex, spinal cord, and amygdala in rats. Reserpine stimulates the degradation of MA from the pool compartment (Slope<sub>1</sub> = 1.1 × 10<sup>-1</sup> h) and the elimination of MA (Slope<sub>2</sub> = 1.25 h) through the transit chain. Regarding the reference dose (1 mg/kg) of the RIM model, the administration of 4 mg/kg would lead to a mean reduction of 65% (C<sub>max</sub>), 80% (C<sub>min</sub>), and 70% (AUC) of MA across the brain regions tested. (4) Conclusions: Regional brain variations in neurotransmitter depletion were identified, particularly in the amygdala, offering insights for therapeutic strategies and biomarker identification in FMS research."],"journal":["Pharmaceutics"],"pubmed_title":["Population Pharmacokinetic-Pharmacodynamic Analysis of a Reserpine-Induced Myalgia Model in Rats."],"pmcid":["PMC11359992"],"funding_grant_id":["GV/2018/049","CIGE/2022/148"],"pubmed_authors":["Valverde-Navarro AA","Gonzalez-Soler EM","Adell A","Alfosea-Cuadrado GM","Blasco-Serra A","Mangas-Sanjuan V","Zarzoso-Foj J"],"additional_accession":[]},"is_claimable":false,"name":"Population Pharmacokinetic-Pharmacodynamic Analysis of a Reserpine-Induced Myalgia Model in Rats.","description":"(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<sup>-1</sup> mL/h/kg). A precursor-pool PK-PD model (k<sub>in</sub> = 6.1 × 10<sup>-3</sup> mg/h, k<sub>p</sub> = 8.6 × 10<sup>-4</sup> h<sup>-1</sup> and k<sub>out</sub> = 2.7 × 10<sup>-2</sup> h<sup>-1</sup>) with a parallel transit chain (k<sub>0</sub> = 1.9 × 10<sup>-1</sup> h<sup>-1</sup>) characterized the longitudinal levels of MA in the prefrontal cortex, spinal cord, and amygdala in rats. Reserpine stimulates the degradation of MA from the pool compartment (Slope<sub>1</sub> = 1.1 × 10<sup>-1</sup> h) and the elimination of MA (Slope<sub>2</sub> = 1.25 h) through the transit chain. Regarding the reference dose (1 mg/kg) of the RIM model, the administration of 4 mg/kg would lead to a mean reduction of 65% (C<sub>max</sub>), 80% (C<sub>min</sub>), and 70% (AUC) of MA across the brain regions tested. (4) Conclusions: Regional brain variations in neurotransmitter depletion were identified, particularly in the amygdala, offering insights for therapeutic strategies and biomarker identification in FMS research.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Aug","modification":"2024-11-09T10:59:30.502Z","creation":"2024-11-09T10:59:30.502Z"},"accession":"S-EPMC11359992","cross_references":{"pubmed":["39204446"],"doi":["10.3390/pharmaceutics16081101"]}}