Hornung N et al. - Clinical efficacy and intracellular methotrexate (MTX) concentrations in erythrocytes (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. Methods
Study to investigate the accumulation of MTX in circulating erythrocytes and the association with pharmacokinetic variables, weekly dose, and clinical efficacy in chronic RA pts (n=76)
40/76 pts were included before initiation of MTX therapy
Laboratory analyses, Ery-MTX, and clinical examinations including toxicity data were performed prospectively for 52 wks
Plasma concs of MTX were measured and AUC was estimated along with other pharmacokinetic variables
Results
Ery-MTX rose after initiation of therapy and reached a steady state after 6-8 wks
The correlation between steady-state Ery-MTX and dose was poor
Steady-state Ery-MTX levels correlated strongly with the estimated AUC
Both steady-state Ery-MTX levels and estimated AUC were higher in pts responding to MTX therapy vs pts classified as nonresponders and were similar to pts on longterm MTX therapy
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