What You Have No Idea About (-)-MK 801 Maleate A 205804

The MTX PK evaluation is summarized in Table 5. Following several dosing of CP 690,550 co administered with single dose MTX, the MTX exposures, AUC24 and Cmax, decreased by 10% and 13%, respectively, when compared with (-)-MK 801 Maleate exposure following administration of MTX alone. The Ae24 and CLR of MTX were decreased by 23% and 14%, respectively, while CL/F increased by 11% and t1/2 was delayed by 0. 5 h.

A 205804 Thirty one of the 34 AEs were mild in intensity and the remaining three were moderate. The three moderate events all occurred in one patient who had a history of migraine. There were two haematological AEs, of anaemia, both in the CP 690,550 plus MTX treatment group and mild in severity. One patient had haemoglobin levels of 11. 8 mg on day 0 and 11. 7 mg after dosing on day 11, and haematocrit levels of 36. 9% on day 0 and 29. 8% on day 11, the second patient had haemoglobin levels of 13. 1 mg on day 0 and 10. 7 mg at follow up, and haematocrit levels of 40. 7% on day 0 and 33. 2% at follow up. Four events reported by two patients in the CP 690,550 treatment group were considered treatment related by the study investigator.

Consequently,the use of MTX in combination with other nonbiological DMARDs has been increasingly investigated. Combination therapy of biological and nonbiological DMARDs A 205804 with MTX has proven to be more effective than monotherapy. Even with this approach, 40?60% of patients fail to achieve signicant improvements in disease activity, therefore, the possibility that combinations of MTX with new agents,such as CP 690,550, will offer superior efcacy and tolerability proles remains, and should be investigated. The results of this study show that co administration of CP 690,550 with MTX had no statistically or clinically signicant effect on the PK prole of CP 690,550. The small changes in MTX PK suggest that no modications to the individualized dosing of MTX are warranted.

MTX therapy can result in haematological AEs and, in a previous study of CP 690,550 in patients with RA, haematological AEs occurred more frequently in the CP 690,550 treatment groups than in the placebo group. While the haematological AEs in the CP 690,550 groups were mostly mild to moderate in severity, and were reversible on cessation of treatment, this observation raises the possibility that co administration of CP 690,550 with MTX could lead to more frequent or severe haematological AEs.