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High Methotrexate Triglutamate Level Is an Independent Predictor of Adverse Effects in Asian Indian Rheumatoid Arthritis Patients-A Preliminary Study.
- Source :
-
Therapeutic drug monitoring [Ther Drug Monit] 2017 Apr; Vol. 39 (2), pp. 157-163. - Publication Year :
- 2017
-
Abstract
- Background: It is unclear whether erythrocyte methotrexate polyglutamate levels (MTX-glun) are associated with response or adverse effects to methotrexate in rheumatoid arthritis. This preliminary study evaluated their utility in Asian Indian patients over 24 weeks.<br />Methods: Rheumatoid arthritis patients were started on oral methotrexate at a dose of 15 mg/wk, which was escalated to 25 mg by 12 weeks and continued till 24 weeks. Erythrocyte (RBC) MTX-glu1 to MTX-glu5 levels (nmol/L RBC) were determined at 4, 8, 16, and 24 weeks by using reverse-phase high-performance liquid chromatography. Area under the concentration curve (AUC) of MTX-glu1-5, MTX-glu3-5, and MTX-glu3 levels was compared between groups with regards to response and adverse effects.<br />Results: This study included 117 patients with mean (SD) age of 42.7 (±11.9) years and disease duration of 2.0 (1.7) years. Mean (SD) RBC MTX-glu1-5 levels at 4, 8, 16, and 24 weeks were 93 (±29), 129 (±46), 143 (±49), and 159 (±65) nmol/L RBC; the highest individual polyglutamate was MTX-glu3 (40%). There was significant correlation between MTX-glu1-5 (r = 0.38, P < 0.001) and MTX-glu3 (r = 0.49, P < 0.001) with methotrexate dose. There was no significant difference of AUC MTX-glun between responders and nonresponders. However, AUC MTX-glu3 was significantly (P = 0.03) higher in patients with adverse effects. On logistic regression, AUC of MTX-glu3 [odds ratio = 1.004 (95% confidence interval 1.002-1.007)] and methotrexate dose at 24 weeks were independent predictors of adverse effects.<br />Conclusions: In this preliminary study, higher levels of RBC MTX-glu3 were found to be the independent predictors for adverse effects in rheumatoid arthritis patients.
- Subjects :
- Administration, Oral
Adult
Antirheumatic Agents blood
Area Under Curve
Arthritis, Rheumatoid blood
Chromatography, High Pressure Liquid methods
Drug-Related Side Effects and Adverse Reactions blood
Erythrocytes chemistry
Female
Humans
Male
Methotrexate administration & dosage
Methotrexate adverse effects
Methotrexate blood
Polyglutamic Acid administration & dosage
Polyglutamic Acid adverse effects
Polyglutamic Acid blood
Antirheumatic Agents administration & dosage
Antirheumatic Agents adverse effects
Arthritis, Rheumatoid drug therapy
Methotrexate analogs & derivatives
Polyglutamic Acid analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 1536-3694
- Volume :
- 39
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Therapeutic drug monitoring
- Publication Type :
- Academic Journal
- Accession number :
- 28107255
- Full Text :
- https://doi.org/10.1097/FTD.0000000000000375