caa a22 4500 477058078 CHVBK 20180405111352.0 cr unu---uuuuu 170330e19960101xx s 000 0 eng 10.1007/BF00226329 doi (NATIONALLICENCE)springer-10.1007/BF00226329 A limited sampling method to estimate methotrexate pharmacokinetics in patients with rheumatoid arthritis using a Bayesian approach and the population data modeling program P-PHARM [Elektronische Daten] [F. Bressolle, L. Edno, C. Bologna, J. Sany, J. Bernard, B. Combe, R. Gomeni] This paper describes a methodology to calculate methotrexate (MTX) pharmacokinetic parameters after intramuscular administration using two samples and the population parameters. Total and free MTX were measured over a 36-h period in 56 rheumatoid arthritis patients; 14 patients were studied after a two-dose scheme at 15-day intervals. The Hill equation was used to relate the free MTX to the total MTX changes in plasma concentrations, and a two-compartment open model was used to fit the total MTX plasma concentrations. A non-linear mixed effect procedure was used to estimate the population parameters and to explore the interindividual variability in relation to the following covariables: age, weight, height, haemoglobin, erythrocyte sedimentation rate, platelet count, creatinine clearance, rheumatoid factor, C-reactive protein, swelling joint count, and Ritchie's articular index. Population parameters were evaluated for 40 patients using a three-step approach. The population average parameters and the interindividual variabilities expressed as coefficients of variation (CV%) were: CL, 6.94 l · h-1 (20.5%); V, 34.8 l (32.2%); k12, 0.0838 h-1 (47.7%); k21, 0.0769 h-1 (61.6%); ka, 4.31 h-1 (58%); Emax, 1.12 μmol · l-1 (19.7%); γ, 0.932 (12.3%); and EC50, 2.14 μmol · l-1 (27.3%). Thirty additional data sets (16 new patients and 14 patients of the previous population but treated on a separate occasion) were used to evaluate the predictive performance of the population parameters. Twelve blood samples were collected from each individual in order to calculate individual parameters using standard fitting procedures. These values were compared to the ones estimated using a Bayesian approach with population parameters as a priori information together with two samples, selected from the individual observations. The results show that the bias was not statistically different from zero and the precision of these parameters was excellent. Springer-Verlag, 1996 Methotrexate nationallicence Rheuma nationallicence Bayesian estimation nationallicence pharmacokinetic parameters nationallicence P-PHARM software nationallicence Bressolle F. Laboratoire de Pharmacocinétique, Faculté de Pharmacie, 15, Ave. Ch. Flahault, F-34060, Montpellier Cedex 01, France aut Edno L. Laboratoire de Pharmacocinétique, Hôpital Carémeau, F-30900, Nîmes, France aut Bologna C. Service d'Immuno-Rhumatologie, Hôpital Gui de Chauliac, F-34000, Montpellier, France aut Sany J. Service d'Immuno-Rhumatologie, Hôpital Gui de Chauliac, F-34000, Montpellier, France aut Bernard J. Service de Rhumatologie, Hôpital Carémeau, F-30900, Nîmes, France aut Combe B. Service de Rhumatologie, Hôpital Carémeau, F-30900, Nîmes, France aut Gomeni R. SIMED, 9-11 Rue Georges Enesco, F-94008, Créteil, France aut European Journal of Clinical Pharmacology Springer-Verlag 49/4(1996-01-01), 285-292 0031-6970 49:4<285 1996 49 228 https://doi.org/10.1007/BF00226329 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00226329 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Bressolle F. Laboratoire de Pharmacocinétique, Faculté de Pharmacie, 15, Ave. Ch. Flahault, F-34060, Montpellier Cedex 01, France aut NATIONALLICENCE 700 1- Edno L. Laboratoire de Pharmacocinétique, Hôpital Carémeau, F-30900, Nîmes, France aut NATIONALLICENCE 700 1- Bologna C. Service d'Immuno-Rhumatologie, Hôpital Gui de Chauliac, F-34000, Montpellier, France aut NATIONALLICENCE 700 1- Sany J. Service d'Immuno-Rhumatologie, Hôpital Gui de Chauliac, F-34000, Montpellier, France aut NATIONALLICENCE 700 1- Bernard J. Service de Rhumatologie, Hôpital Carémeau, F-30900, Nîmes, France aut NATIONALLICENCE 700 1- Combe B. Service de Rhumatologie, Hôpital Carémeau, F-30900, Nîmes, France aut NATIONALLICENCE 700 1- Gomeni R. SIMED, 9-11 Rue Georges Enesco, F-94008, Créteil, France aut NATIONALLICENCE 773 0- European Journal of Clinical Pharmacology Springer-Verlag 49/4(1996-01-01), 285-292 0031-6970 49:4<285 1996 49 228 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer