TY - JOUR
T1 - Methotrexate pharmacokinetic is influenced by co-administration of cyclosporin in rheumatoid arthritis patients. Results from a randomized clinical trial
AU - Odderskov, Caroline
AU - Stengaard-Pedersen, Kristian
AU - Ellingsen, Torkell
AU - Hornung, Nete
PY - 2020/4
Y1 - 2020/4
N2 - The aim was to investigate if the pharmacokinetics of methotrexate (MTX) are affected by the addition of cyclosporin (CsA). Forty patients diagnosed with early rheumatoid arthritis (RA) were included in this open prospective study: 20 patients were treated with a dose of 7.5 mg MTX and a dose of 2.5 mg/kg CsA, 20 patients were treated with a dose of 7.5 mg MTX and placebo. Baseline measurements of plasma MTX and erythrocyte MTX were made. Area under the plasma concentration versus time curve (AUC) and other pharmacokinetic variables were estimated by means of a population based software model. Clinical improvement of 20–50–70% according to the American College of Rheumatology (ACR) and adverse events were evaluated ongoing for 52 weeks. We found that mean peak plasma MTX concentration was significantly higher in the MTX + CsA combination treatment group (p =.003). No differences in AUC, erythrocyte MTX or other pharmacokinetic parameters were found between the two treatment groups. Estimated Glomerular Filtration Rate (eGFR) decreased significantly in the MTX + CsA treatment group (p <.001), but no serious adverse events occurred in either of the two groups. In conclusion, CsA added to methotrexate treatment in early RA significantly increased peak-plasma MTX concentration, but other pharmacokinetic parameters and measurements of MTX were unchanged.
AB - The aim was to investigate if the pharmacokinetics of methotrexate (MTX) are affected by the addition of cyclosporin (CsA). Forty patients diagnosed with early rheumatoid arthritis (RA) were included in this open prospective study: 20 patients were treated with a dose of 7.5 mg MTX and a dose of 2.5 mg/kg CsA, 20 patients were treated with a dose of 7.5 mg MTX and placebo. Baseline measurements of plasma MTX and erythrocyte MTX were made. Area under the plasma concentration versus time curve (AUC) and other pharmacokinetic variables were estimated by means of a population based software model. Clinical improvement of 20–50–70% according to the American College of Rheumatology (ACR) and adverse events were evaluated ongoing for 52 weeks. We found that mean peak plasma MTX concentration was significantly higher in the MTX + CsA combination treatment group (p =.003). No differences in AUC, erythrocyte MTX or other pharmacokinetic parameters were found between the two treatment groups. Estimated Glomerular Filtration Rate (eGFR) decreased significantly in the MTX + CsA treatment group (p <.001), but no serious adverse events occurred in either of the two groups. In conclusion, CsA added to methotrexate treatment in early RA significantly increased peak-plasma MTX concentration, but other pharmacokinetic parameters and measurements of MTX were unchanged.
KW - cyclosporine
KW - methotrexate
KW - pharmacokinetic
KW - Rheumatoid arthritis
UR - http://www.scopus.com/inward/record.url?scp=85077390193&partnerID=8YFLogxK
U2 - 10.1080/00365513.2019.1706190
DO - 10.1080/00365513.2019.1706190
M3 - Journal article
C2 - 31876200
AN - SCOPUS:85077390193
SN - 0036-5513
VL - 80
SP - 185
EP - 190
JO - Scandinavian Journal of Clinical and Laboratory Investigation
JF - Scandinavian Journal of Clinical and Laboratory Investigation
IS - 3
ER -