title: Population pharmacokinetic modeling of trans-resveratrol and its glucuronide and sulfate conjugates after oral and intravenous administration in rats.
abstract: OBJECTIVE
  To develop a population pharmacokinetic (PK) model which allowed the simultaneous modeling of trans-resveratrol and its glucuronide and sulfate conjugates.
  
  
  METHODS
  Male Sprague-Dawley rats were administered i.v. and p.o. with 2, 10 and 20 mg·kg(-1) of trans-resveratrol. Blood was collected at different times during 24 h. An integrated PK model was developed using a sequential analysis, with non-linear mixed effect modeling (NONMEM). A prediction-corrected visual predictive check (pcVPC) was used to assess model performance. The model predictive capability was also evaluated with simulations after the i.v. administration of 15 mg·kg(-1) that were compared with an external data set.
  
  
  RESULTS
  Disposition PK of trans-resveratrol and its metabolites was best described by a three-linked two-compartment model. Clearance of trans-resveratrol by conversion to its conjugates occurred by a first-order process, whereas both metabolites were eliminated by parallel first-order and Michaelis-Menten kinetics. The pcVPC confirmed the model stability and precision. The final model was successfully applied to the external data set showing its robustness.
  
  
  CONCLUSIONS
  A robust population PK model has been built for trans-resveratrol and its glucuronide and sulfate conjugates that adequately predict plasmatic concentrations.
authors: Departament de Farmàcia i Tecnologia Farmacèutica Facultat de Farmàcia, Universitat de Barcelona, Av. Joan XXIII s/n, 08028, Barcelona, Spain. helena.colom@ub.edu
authors: Helena
authors: H
authors: Colom
authors: Irene
authors: I
authors: Alfaras
authors: Mònica
authors: M
authors: Maijó
authors: M Emília
authors: ME
authors: Juan
authors: Joana M
authors: JM
authors: Planas
mesh_terms: D000284:Administration, Oral; D000818:Animals; D020719:Glucuronides / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D008297:Male; D008956:Models, Chemical; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013431:Sulfates / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D020719:Glucuronides; D013267:Stilbenes; D013431:Sulfates; D014665:Vasodilator Agents; D000077185:Resveratrol