Pharmacokinetics of oral methotrexate in patients with rheumatoid arthritis
| Autor: | Murray L. Barclay, Peter T. Chapman, Lisa K. Stamp, John L. O'Donnell, Judith M. Dalrymple, Mei Zhang |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Adult
Male medicine.medical_specialty Erythrocytes Immunology Individuality Arthritis Administration Oral Gastroenterology Arthritis Rheumatoid Rheumatology Pharmacokinetics Oral administration Internal medicine medicine Immunology and Allergy Humans Pharmacology (medical) Chromatography High Pressure Liquid Aged business.industry Half-life Middle Aged medicine.disease Surgery Methotrexate Polyglutamic Acid Rheumatoid arthritis Female business medicine.drug Blood sampling Half-Life |
| Zdroj: | Arthritis and rheumatism. 58(11) |
| ISSN: | 0004-3591 |
| Popis: | Objective There is evidence supporting a therapeutic range for methotrexate polyglutamate (MTXGlu) concentrations in the treatment of rheumatoid arthritis (RA). Knowledge of the pharmacokinetics of MTXGlu1–5 is required for optimal timing of blood sampling. The aim of this study was to determine the time to steady state and the half-life of accumulation of red blood cell (RBC) MTXGlu1–5 in patients with RA commencing oral MTX, and the time for RBC MTXGlu1–5 to become undetectable and the half-life of elimination of RBC MTXGlu1–5 in patients ceasing treatment with oral MTX. Methods Ten patients beginning treatment and 10 patients stopping treatment with low-dose oral MTX were recruited. Blood samples were initially collected weekly, with gradual extension to monthly collection over the study period. RBC MTXGlu1–5 concentrations were assayed by high-performance liquid chromatography. Results were analyzed using a first-order exponential method. Results The median times to reach steady state in RBCs (defined as 90% of the maximum concentration) were 6.2, 10.6, 41.2, 149, and 139.8 weeks, respectively, for MTXGlu1, MTXGlu2, MTXGlu3, MTXGlu4, and MTXGlu5. The median half-life of accumulation for RBC MTXGlu1–5 ranged from 1.9 weeks to 45.2 weeks. The median times for MTXGlus to become undetectable in RBCs were 4.5, 5.5, 10, 6, and 4 weeks, respectively, for MTXGlu1, MTXGlu2, MTXGlu3, MTXGlu4, and MTXGlu5. The median half-life of elimination for RBC MTXGlu1–5 ranged from 1.2 weeks to 4.3 weeks. Conclusion There is wide interpatient variability of RBC MTXGlu1–5 accumulation and elimination in adults with RA. These data also suggest that after a dose change, >6 months are required for RBC MTXGlu1–5 to reach steady state. Such delays in achieving steady state suggest that more rapid dose escalation or subcutaneous administration from the outset should be considered. |
| Databáze: | OpenAIRE |
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