Effect of YM294, recombinant human interleukin-11, on carboplatin-induced thrombocytopenia in rats.
We investigated the effects of YM294, recombinant human interleukin-11, on changes in blood cell levels in carboplatin-treated rats. Continuous infusion of YM294 was carried out by either intravenous or subcutaneous injection (10 and 100 micrograms/rat/day) for 14 days via an implanted osmotic pump. Carboplatin (30 mg/kg iv) significantly decreased platelet counts on days 7-9; counts subsequently increased to levels greater than the initial level by day 21. Intravenous administration of YM294 inhibited this decrease in platelet count by carboplatin and increased the platelet count in the recovery phase in a dose-dependent manner. YM294 also showed effects on carboplatin-induced changes in white blood cell and red blood cell counts; these effects seemed, however, to be neither consistent nor dose-dependent. The effects of YM294 on subcutaneous infusion were similar to those on intravenous infusion. The effect of YM294 on the survival of rats treated with a higher dose of carboplatin (60 mg/kg iv) was also investigated. YM294 (100 micrograms/rat/day) given by continuous intravenous infusion increased the 30-day survival rate. These results confirm the utility of YM294 in the treatment of thrombocytopenia after chemotherapy.
Taguchi
K
K
Clinical Pharmacology Research Laboratories, Institute for Drug Development Research, Yamanouchi Pharmaceutical Co., Ltd., Tokyo, Japan.
Asano
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D016190:Carboplatin / Q000633:toxicity*; D017370:Interleukin-11 / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D013921:Thrombocytopenia / Q000139:chemically induced / Q000517:prevention & control*
D000970:Antineoplastic Agents; D017370:Interleukin-11; D011994:Recombinant Proteins; D016190:Carboplatin