title: Validation of a simple HPLC-UV method for rifampicin determination in plasma: Application to the study of rifampicin arteriovenous concentration gradient.
abstract: In clinical practice, rifampicin exposure is estimated from its concentration in venous blood samples. In this study, we hypothesized that differences in rifampicin concentration may exist between arterial and venous plasma. An HPLC-UV method for determining rifampicin concentration in plasma using rifapentine as an internal standard was validated. The method, which requires a simple protein precipitation procedure as sample preparation, was performed to compare venous and arterial plasma kinetics after a single therapeutic dose of rifampicin (8.6 mg/kg i.v, infused over 30 min) in baboons (n=3). The method was linear from 0.1 to 40 μg mL(-1) and all validation parameters fulfilled the international requirements. In baboons, rifampicin concentration in arterial plasma was higher than in venous plasma. Arterial Cmax was 2.1±0.2 fold higher than venous Cmax. The area under the curve (AUC) from 0 to 120 min was ∼80% higher in arterial plasma, indicating a significant arteriovenous concentration gradient in early rifampicin pharmacokinetics. Arterial and venous plasma concentrations obtained 6h after rifampicin injection were not different. An important arteriovenous equilibration delay for rifampicin pharmacokinetics is reported. Determination in venous plasma concentrations may considerably underestimate rifampicin exposure to organs during the distribution phase.
authors.affiliation: IMIV, CEA, Inserm, CNRS, Univ. Paris-Sud, Université Paris Saclay, CEA-SHFJ, Orsay, France. Electronic address: sebastien.goutal@cea.fr.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Goutal
authors.affiliation: IMIV, CEA, Inserm, CNRS, Univ. Paris-Sud, Université Paris Saclay, CEA-SHFJ, Orsay, France; Variabilité de réponse aux psychotropes, INSERM, U1144, 75006 Paris, France; Université Paris Descartes, UMR-S 1144, Paris F-75006, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Auvity
authors.affiliation: Laboratoire de Pharmacologie-Toxicologie, Assistance Publique des Hôpitaux de Paris, Hôpitaux Universitaires Henri Mondor, 94000 Créteil, France.
authors.forename: Tiphaine
authors.initials: T
authors.lastname: Legrand
authors.affiliation: LICSEN, NIMBE, CEA, CNRS, Université Paris-Saclay, CEA Saclay 91191 Gif-sur-Yvette Cedex, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Hauquier
authors.affiliation: Variabilité de réponse aux psychotropes, INSERM, U1144, 75006 Paris, France; Université Paris Descartes, UMR-S 1144, Paris F-75006, France.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cisternino
authors.affiliation: Variabilité de réponse aux psychotropes, INSERM, U1144, 75006 Paris, France; Université Paris Descartes, UMR-S 1144, Paris F-75006, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Chapy
authors.affiliation: IMIV, CEA, Inserm, CNRS, Univ. Paris-Sud, Université Paris Saclay, CEA-SHFJ, Orsay, France.
authors.forename: Wadad
authors.initials: W
authors.lastname: Saba
authors.affiliation: IMIV, CEA, Inserm, CNRS, Univ. Paris-Sud, Université Paris Saclay, CEA-SHFJ, Orsay, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tournier
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001158:Arteries / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D007700:Kinetics; D008297:Male; D010215:Papio; D010949:Plasma / Q000737:chemistry*; D015203:Reproducibility of Results; D012293:Rifampin / Q000031:analogs & derivatives / Q000097:blood* / Q000737:chemistry* / Q000493:pharmacokinetics; D013056:Spectrophotometry, Ultraviolet / Q000379:methods*; D014680:Veins / Q000378:metabolism*
chemical_list: D012293:Rifampin; C018421:rifapentine
keywords: Arterial; Arteriovenous differences; Nonhuman primate; Organic anion transporting polypeptide; Pharmacokinetics; Rifampin