Population pharmacokinetic investigation of low-dose methotrexate in rheumatoid arthritics Japanese patients.
OBJECTIVE: To estimate the population pharmacokinetics of low-dose methotrexate (MTX) in Japanese patients using nonmem, a computer program designed for analysing drug pharmacokinetics in study populations through pooling of data. METHOD: A total of 153 serum concentration measurements obtained from...
| Publicado en: | Journal of Clinical Pharmacy & Therapeutics Vol. 32; no. 6; pp. 573 - 579 |
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| Autores principales: | , , , |
| Formato: | research Journal Article |
| Publicado: |
Wiley-Blackwell
Dec2007
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=105844905&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 105844905 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 02694727 EV4 jtl: Journal of Clinical Pharmacy & Therapeutics issn: 02694727 maglogo: Y pubinfo: dt: Dec2007 vid: 32 iid: 6 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 105844905 2009721582 10.1111/j.1365-2710.2007.00859.x NLM18021334 105844905 ppf: 573 ppct: 6 formats: fmt: @attributes: type: P tig: atl: Population pharmacokinetic investigation of low-dose methotrexate in rheumatoid arthritics Japanese patients. aug: au: Yukawa E. Mori S Ueda K Nakada Y affil: Laboratory of Evidence-based Pharmacotherapy, College of Pharmaceutical Sciences, Daiichi University, Minami-Ku, Fukuoka, Japan sug: subj: Antirheumatic Agents Pharmacokinetics Arthritis, Rheumatoid Drug Therapy Methotrexate Pharmacokinetics Adult Female Male Models, Biological Human Adult: 19-44 years Female Male ab: OBJECTIVE: To estimate the population pharmacokinetics of low-dose methotrexate (MTX) in Japanese patients using nonmem, a computer program designed for analysing drug pharmacokinetics in study populations through pooling of data. METHOD: A total of 153 serum concentration measurements obtained from the 17 healthy volunteers and 17 patients with rheumatoid arthritis were collected. Analysis of the pharmacokinetics of MTX was accomplished using a two-compartment pharmacokinetic model with first-order absorption. The effect of a variety of developmental and demographic factors on MTX disposition was investigated. RESULTS: The final pharmacokinetic parameters were CL/F (L/kg/h) = 0.177 x 0.394MULT, V1/F (L/kg) = 0.0501, Q/F (L/kg/h) = 0.056, V2/F (L/kg) = 0.368, ka (h-1) = 0.503, where CL is total body clearance, V1 and V2 is apparent volume of distribution in the central and peripheral compartments, k(a) is absorption rate constant, Q is intercompartmental clearance and MULT = 1 for patients received multiple dosing and zero otherwise. The interindividual variabilities in CL, Q and V1 were 25.7%, 22.3% and 217.9%, respectively, and the residual variability was 17.8% as a coefficient of variation. Because of the lake of information on data set we were unable to characterize the interindividual variability for V2 and ka. CONCLUSION: Clinical application of the model to patient care may permit selection of an appropriate dosage to achieve target MTX concentrations, thus enabling the clinician to achieve the desired therapeutic effect in Japanese patients. However, the MTX dosage regimen for the individual patient should be based on a careful appraisal of their clinical need for the drug. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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