title: Effect of gender and CYP2C9 and CYP2C8 polymorphisms on the pharmacokinetics of ibuprofen enantiomers.
abstract: OBJECTIVE
  To evaluate the effect of polymorphisms in CYP2C9 and CYP2C8 and gender on the pharmacokinetics of the enantiomeric forms of ibuprofen.
  
  
  METHODS
  122 healthy volunteers were genotyped for polymorphisms in CY2C8 and CYP2C9 using real-time PCR.
  
  
  RESULTS
  CYP2C8 polymorphisms affected neither R- nor S-ibuprofen. CYP2C9*3 and CYP2C9*2 carriers had a lower S-ibuprofen clearance and a higher S-ibuprofen AUC and half-life. R-ibuprofen clearance was decreased in CYP2C9*3 carriers. Gender affected R-ibuprofen and S-ibuprofen pharmacokinetics. Multiple regression analysis showed that CYP2C9*2, CYP2C9*3 and gender were associated with S-ibuprofen clearance, but only CYP2C9*3 was associated with R-ibuprofen clearance.
  
  
  CONCLUSIONS
  The pharmacokinetics of S-ibuprofen and R-ibuprofen is affected by CYP2C9 polymorphisms and gender. CYP2C8 polymorphisms do not have a significant role. Original submitted 6 February 2015; Revision submitted 1 April 2015.
authors.affiliation: Clinical Pharmacology Service, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, Instituto de Investigación Sanitaria Princesa (IP), Diego de León 62, 28006 Madrid, Spain.
authors.forename: Dolores
authors.initials: D
authors.lastname: Ochoa
authors.affiliation: Clinical Pharmacology Service, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, Instituto de Investigación Sanitaria Princesa (IP), Diego de León 62, 28006 Madrid, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Prieto-Pérez
authors.affiliation: Clinical Pharmacology Service, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, Instituto de Investigación Sanitaria Princesa (IP), Diego de León 62, 28006 Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Román
authors.affiliation: Clinical Pharmacology Service, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, Instituto de Investigación Sanitaria Princesa (IP), Diego de León 62, 28006 Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Talegón
authors.affiliation: Clinical Pharmacology Service, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, Instituto de Investigación Sanitaria Princesa (IP), Diego de León 62, 28006 Madrid, Spain.
authors.forename: Angela
authors.initials: A
authors.lastname: Rivas
authors.affiliation: Fundación Teófilo Hernando, Parque Científico de Madrid - Edificio CLAID, C/Faraday 7 - Campus de Cantoblanco, 28049 Madrid, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Galicia
authors.affiliation: Clinical Pharmacology Service, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, Instituto de Investigación Sanitaria Princesa (IP), Diego de León 62, 28006 Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, C/Monforte de Lemos 3-5, 28029 Madrid, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Abad-Santos
authors.affiliation: Clinical Pharmacology Service, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, Instituto de Investigación Sanitaria Princesa (IP), Diego de León 62, 28006 Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, C/Monforte de Lemos 3-5, 28029 Madrid, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Cabaleiro
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065727:Cytochrome P-450 CYP2C8 / Q000235:genetics*; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006207:Half-Life; D006801:Humans; D007052:Ibuprofen / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D013237:Stereoisomerism; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C450259:CYP2C8 protein, human; D065727:Cytochrome P-450 CYP2C8; D007052:Ibuprofen
keywords: CYP2C8; CYP2C9; ibuprofen; pharmacokinetics; polymorphisms