[Clinical tolerance test of recombinant human thrombopoietin]

To evaluate the safety of domestic recombinant human thrombopoietin (rhTPO) in human body and the its effects on hemogram and platelet function, and induction of anti-rhTPO antibody.

In the single dose tolerance test, twenty-seven healthy volunteers were randomly divided into 4 groups. rhTPO was injected subcutaneously at the doses of 0.25 microg/kg, 0.5 microg/kg, 1 microg/kg, and 2 microg/kg respectively. In the multiple dose tolerance test, 7 patients with non-Hodgkin lymphoma or acute leukemia after chemotherapy received rhTPO at the dose of 1.0 microg/kg for 7 - 14 days. The symptoms (if any), complete blood count, platelet aggregation test, serum chemistry, and anti-rhTPO antibody were followed serially.

Out of the 27 healthy volunteers receiving single dose of rhTPO, one showed transient increase of body temperature to 37.4 degrees C six hours after the injection; one felt mild fatigue, anorexia, and somnolence the day after injection, and one showed transient elevation of alanine transminase (ALT) and asparate aminotransferase (AST) levels. Single dose administration of rhTPO at the doses of 0.5 microg/kg, 1.0 microg/kg, and 2.0 microg/kg was associated dose-dependently with 24% - 52% increase of platelet count, peaking at the day 14 and returning to the baseline Level by, day 21. No abnormality was observed in aggregation function when the platelet count peaked. Single dose administration of rhTPO showed no influence on red blood cells and white blood cells. In the multiple dose group, rhTPO at the dose of 1.0 microg x kg(-1) x d(-1) for 7 - 14 days was well tolerated by patients with hemotological malignancies. One patient developed transient slight elevation of serum ALT and AST. After the treatment with rhTPO, platelet counts increased to some extent in 4 patients. Low titer (1:5) of anti-rhTPO antibody was found transiently in one patient.

A single bolus subcutanenous injection of 0.25 - 2.0 microg/kg rhTPO and daily subcutaneous injection of 1.0 microg/kg rhTPO for 7 - 14 days are well tolerated by human beings and without significant adverse effect. rhTPO increases peripheral platelet count and has no effect on aggregation function. Circulating anti-rhTPO antibody occurs after multiple administration of rhTPO. However, its clinical significance remains to be studied.