A multi-institutional study may offer clues for the treatment of some autoimmun...( Guo pools due to variation of cell turn...)

Guo pools due to variation of cell turnover in these individuals. The plasma terminal half-life of BCX-1777 was 11.7 hr, but the half-life of the inhibition of erythrocyte PNP was much longer. In vitro experiments indicated that it might be as long as five days.

During and 7-10 days following the dosing periods, most treated patients have shown large and rapid increase in blood levels of deoxyguanosine, rapid accumulation of dGTP in leukemic T-cells, and a sharp drop in leukemic cell counts. Oral administration of 10 mg/m² BCX-1777 solution to humans also produced an increase in plasma dGuo and inhibition of erythrocyte PNP with an apparent bioavailability of approximately 30 percent.

Conclusions

These preliminary data confirm the hypothesis that use of the PNP inhibitor BCX-1777 to elevate plasma dGuo results in elevation of cellular dGTP and a corresponding reduction of leukemic T-cells. An evaluation of the clinical efficacy is scheduled to be determined in several Phase II clinical trials. Additionally, these data support use of PNP inhibitors in treatment of other T-cell proliferative disorders, such as psoriasis and rhematoid arthritis.

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Contact: Donna Krupa
djkrupa1@aol.com
703-527-7357
American Physiological Society
19-Apr-2004

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