10741
document
Combination therapy with methotrexate and hydroxychloroquine for rheumatoid arthritis increases exposure to methotrexate . 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 .
10742
Intervention_Pharmacological
methotrexate and hydroxychloroquine
10743
Intervention_Pharmacological
methotrexate ( MTX )
10744
Intervention_Pharmacological
hydroxychloroquine ( HCQ )
10745
Intervention_Pharmacological
MTX
10746
Intervention_Pharmacological
HCQ
10747
Intervention_Pharmacological
MTX
10748
Intervention_Pharmacological
MTX
10749
Intervention_Pharmacological
HCQ
10750
Intervention_Pharmacological
MTX
10751
Intervention_Pharmacological
HCQ
10752
Intervention_Pharmacological
MTX
10753
Intervention_Pharmacological
MTX
10754
Intervention_Pharmacological
MTX
10755
Intervention_Pharmacological
HCQ
10756
Intervention_Pharmacological
MTX
10757
Intervention_Pharmacological
HCQ
10758
Intervention_Pharmacological
HCQ
10759
Intervention_Pharmacological
MTX-HCQ
10760
Intervention_Pharmacological
MTX
10761
Intervention_Pharmacological
MTX
10762
Intervention_Pharmacological
HCQ
10763
Intervention_Pharmacological
MTX
10764
Intervention_Pharmacological
MTX
10765
Intervention_Pharmacological
HCQ
10766
Outcome_Other
concentration-time curve ( AUC )
10767
Outcome_Other
mean AUC for MTX
10768
Outcome_Other
maximum MTX concentration ( Cmax )
10769
Outcome_Other
time to reach Cmax for MTX administration , tmax
10770
Participant_Condition
rheumatoid arthritis
10771
Participant_Sample-size
10
10772
Participant_Condition
healthy