A pharmacokinetic study of idarubicin in Japanese patients with malignant lymphoma: Relationship with leukocytopenia and neutropenia

To clarify the pharmacokinetic properties of idarubicin (IDA) in Japanese p atients and to clarify the relationship between the pharmacokinetic paramet ers of IDA or idarubicinol (IDAol), an active metabolite of IDA, and leukoc ytopenia or neutropenia, we examined the pharmacokinetics of IDA in patient s with malignant lymphoma. Nine of 21 patients registered in an early phase II study of IDA were enrolled in the pharmacokinetic study. IDA (12 or 15 mg/m(2)) was administered by intravenous infusion for 5 minutes. The elimin ation half lives (t(1/2)) of IDA were 11.0 hours and 12.5 hours after admin istration of 12 and 15 mg/m(2) IDA, respectively. IDAol appeared rapidly bo th in plasma and in blood cells, and its concentrations exceeded those of I DA within 4 hours. IDAol had a very long t(1/2) (69.2 hours and 70.0 hours for 12 and 15 mg/m(2), respectively). The areas under the concentration cur ves of IDAol in plasma were 3.4 and 5.8 times higher than those of IDA afte r administration of 12 and 15 mg/m2 IDA, respectively. The t(1/2) of IDAol in plasma correlated significantly with the nadir of neutrophils, and the s teady-state volume of distribution of IDA in plasma and in blood cells corr elated significantly with the nadirs of white blood cells and neutrophils. These results suggest that both IDA and IDAol play an important role in leu kocytopenia or neutropenia. No substantial differences between Japanese and Caucasian people in the pharmacokinetics of IDA were apparent. (C) 2001 Th e Japanese Society of Hematology.