Effect of recombinant human thrombopoietin in nonhuman primates with chemotherapy-induced thrombocytopenia.
We examined the effects of recombinant human thrombopoietin (rhTPO) on myelosuppressive chemotherapy-induced thrombocytopenia in cynomolgus monkeys. After treatment with nimustine (ACNU) on day 0, the monkeys intravenously received rhTPO at a dose of 0.04, 0.2 or 1 microgram/kg/d or monkey's serum once each day from day 1 to day 28. Administration of rhTPO reduced the severity of thrombocytopenia and accelerated the rate of platelet recovery in a dose-dependent fashion. Treatment with the highest rhTPO dose completely prevented thrombocytopenia and stimulated a marked increase in platelet counts over the normal values. Animals treated with ACNU also became neutropenic and slightly anaemic. Administration of rhTPO following ACNU treatment significantly improved neutropenia with increasing doses of rhTPO, but had no effect on anaemia. Compared to the control animals, rhTPO-treated animals exhibited no significant changes in several serum parameters. C-reactive protein concentration and some blood coagulation profiles within the study period. These results suggest a therapeutic efficacy of rhTPO in improving chemotherapy-induced thrombocytopenia.
Akahori
H
H
Pharmaceutical Research Laboratory, Kirin Brewery Co. Ltd, Gunma, Japan.
Shibuya
K
K
Obuchi
M
M
Nishizawa
Y
Y
Tsuji
A
A
Kabaya
K
K
Kusaka
M
M
Ohashi
H
H
Tsumura
H
H
Kato
T
T
Miyazaki
H
H
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001777:Blood Coagulation; D006801:Humans; D007958:Leukocyte Count; D008252:Macaca fascicularis; D008297:Male; D009504:Neutrophils; D015376:Nimustine / Q000009:adverse effects*; D010976:Platelet Count; D011994:Recombinant Proteins / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000139:chemically induced*; D013926:Thrombopoietin / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D015376:Nimustine; D013926:Thrombopoietin