Document Detail


Patients with rheumatoid arthritis treated with methotrexate (MTX): concentrations of steady-state erythrocyte MTX correlate to plasma concentrations and clinical efficacy.
MedLine Citation:
PMID:  18634162     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To investigate the accumulation of methotrexate (MTX) in circulating erythrocytes and the association with pharmacokinetic variables, weekly dose, and clinical efficacy in 2 cohorts of patients with chronic active rheumatoid arthritis (RA) undergoing MTX monotherapy. METHODS: Seventy-six patients with RA were included in this open prospective study: 40 were included before initiation of MTX therapy. Laboratory analyses, intracellular MTX concentrations in erythrocytes (Ery-MTX), and clinical examinations including toxicity data were performed prospectively for 52 weeks. Plasma concentrations of MTX were measured and area under the plasma concentration versus time curve (AUC) was estimated along with other pharmacokinetic variables in a population based software model. RESULTS: Ery-MTX rose after initiation of therapy and reached a steady state after 6-8 weeks. The correlation between steady-state Ery-MTX and dose was poor (r(2) = 0.16), whereas steady-state Ery-MTX levels correlated strongly with the estimated AUC (r(2) = 0.51, log-transformed variables). Both steady-state Ery-MTX levels and estimated AUC were significantly higher in patients responding to MTX therapy than in patients classified as nonresponders according to American College of Rheumatology core criteria and were similar to patients on longterm MTX therapy. CONCLUSION: Our results indicate that clinical efficacy and Ery-MTX may have a causal relation and that measurement of Ery-MTX or estimation of AUC in a software model provides useful guidelines to the clinician when starting MTX therapy in patients with RA. The latter can be performed immediately after initiation of therapy.
Authors:
Nete Hornung; Torkell Ellingsen; J?rn Attermann; Kristian Stengaard-Pedersen; J?rgen Hjelm Poulsen
Publication Detail:
Type:  Journal Article     Date:  2008-07-15
Journal Detail:
Title:  The Journal of rheumatology     Volume:  35     ISSN:  0315-162X     ISO Abbreviation:  J. Rheumatol.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-09-11     Completed Date:  2008-12-11     Revised Date:  2010-03-23    
Medline Journal Info:
Nlm Unique ID:  7501984     Medline TA:  J Rheumatol     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  1709-15     Citation Subset:  IM    
Affiliation:
Department of Clinical Biochemistry, Aarhus University Hospital, University of Aarhus, Aarhus, Denmark. neh@rc.aaa.dk
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MeSH Terms
Descriptor/Qualifier:
Antirheumatic Agents / pharmacokinetics*,  therapeutic use
Area Under Curve
Arthritis, Rheumatoid / drug therapy,  metabolism*,  physiopathology
Cohort Studies
Dose-Response Relationship, Drug
Erythrocytes / metabolism*
Female
Health Status
Humans
Male
Methotrexate / pharmacokinetics*,  therapeutic use
Middle Aged
Models, Biological
Prospective Studies
Severity of Illness Index
Treatment Outcome
Chemical
Reg. No./Substance:
0/Antirheumatic Agents; 59-05-2/Methotrexate

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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