title: Population pharmacokinetics of maslinic acid, a triterpene from olives, after intravenous and oral administration in rats.
abstract: METHODS
  Maslinic acid is a bioactive minor component of Olea europaea L. with health-enhancing activities and no harmful effects. A pharmacokinetic (PK) study was conducted to determine its bioavailability for future studies of maslinic acid in humans.
  
  
  RESULTS
  Intravenous (1 mg/kg) and oral (50 mg/kg) administrations to Sprague-Dawley rats were performed. Blood was obtained several times over 24 h and PKs were analyzed with NONMEM 7.2, applying a population approach. Body weight was included a priori in the model with fixed allometric exponents, based on allometric principles. Plasma concentrations versus time were best characterized by a two-open compartment model with first-order absorption and linear elimination. Maslinic acid had a relative rapid oral absorption with a peak concentration after administration at 0.51 h and a bioavailability of 5.13%. Once in bloodstream, it distributed extensively into tissues, since the central and peripheral distribution volumes were 8.41 L/70 kg and 63.6 L/70 kg, respectively. The clearance (8 L/h/70 kg) was related to unaltered renal excretion. The prediction-corrected visual predictive check confirmed its stability and predictive ability.
  
  
  CONCLUSIONS
  An allometric population PK model was performed for maslinic acid, which adequately described and predicted plasma concentrations.
authors.affiliation: Departament de Fisiologia and Institut de Recerca en Nutrició i Seguretat Alimentària (INSA-UB), Universitat de Barcelona, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Sánchez-González
authors.forename: Helena
authors.initials: H
authors.lastname: Colom
authors.forename: Glòria
authors.initials: G
authors.lastname: Lozano-Mena
authors.forename: M Emília
authors.initials: ME
authors.lastname: Juan
authors.forename: Joana M
authors.initials: JM
authors.lastname: Planas
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000097:blood / Q000191:economics / Q000493:pharmacokinetics*; D001682:Biological Availability; D001835:Body Weight; D019587:Dietary Supplements; D004355:Drug Stability; D005525:Food-Processing Industry / Q000191:economics; D005638:Fruit / Q000737:chemistry*; D007220:Industrial Waste / Q000032:analysis / Q000191:economics; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D008297:Male; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D031658:Olea / Q000737:chemistry*; D017207:Rats, Sprague-Dawley; D065667:Renal Elimination; D014018:Tissue Distribution; D014315:Triterpenes / Q000008:administration & dosage / Q000097:blood / Q000191:economics / Q000493:pharmacokinetics*; D009828:Oleanolic Acid / Q000031:analogs & derivatives
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D007220:Industrial Waste; D014315:Triterpenes; C412811:maslinic acid; D009828:Oleanolic Acid
keywords: HPLC-MS; Maslinic acid; Oral bioavailability; Pentacyclic triterpenes; Rat plasma