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Abstract

Combination therapy with methotrexate and hydroxychloroquine for rheumatoid arthritis increases exposure to methotrexate.

Samantha J Carmichael, Joanne Beal, Richard O Day and Susan E Tett
The Journal of Rheumatology October 2002, 29 (10) 2077-2083;
Samantha J Carmichael
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Joanne Beal
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Richard O Day
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Susan E Tett
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Abstract

OBJECTIVE: To examine the bioavailability of methotrexate (MTX) in the presence of hydroxychloroquine (HCQ), and vice versa, to determine a possible pharmacokinetic explanation for the observation that combination treatment of rheumatoid arthritis with MTX and HCQ has been shown, clinically, to be more potent than MTX used alone. METHODS: In a randomized crossover study, 10 healthy subjects received, on each of 5 dosing occasions, MTX alone as tablets or intravenous solution, HCQ alone as a tablet or oral solution, or a coadministered dose of MTX tablets with an HCQ tablet. The area under the concentration-time curve (AUC) was determined for each subject, on each dosing occasion, for each compound. RESULTS: The mean AUC for MTX was increased (p = 0.005) and the maximum MTX concentration (Cmax) decreased (p = 0.025) when MTX was coadministered with HCQ, compared to MTX administered alone. The time to reach Cmax for MTX administration, tmax, was also increased during the coadministration with HCQ (p = 0.072). The AUC of HCQ showed no significant difference (p = 0.957) between any of the dosing occasions. CONCLUSION: These results may explain the increased potency of the MTX-HCQ combination over MTX as a single agent and also the sustained effects of MTX when administered with HCQ. In addition, the reduced Cmax of MTX observed during the coadministration may explain diminution of acute liver adverse effects. Extra vigilance for MTX adverse effects during combination therapy with HCQ is recommended, especially if renal function is known to be decreased.

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The Journal of Rheumatology
Vol. 29, Issue 10
1 Oct 2002
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Combination therapy with methotrexate and hydroxychloroquine for rheumatoid arthritis increases exposure to methotrexate.
Samantha J Carmichael, Joanne Beal, Richard O Day, Susan E Tett
The Journal of Rheumatology Oct 2002, 29 (10) 2077-2083;

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Combination therapy with methotrexate and hydroxychloroquine for rheumatoid arthritis increases exposure to methotrexate.
Samantha J Carmichael, Joanne Beal, Richard O Day, Susan E Tett
The Journal of Rheumatology Oct 2002, 29 (10) 2077-2083;
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