A Pharmacokinetic Study of Idarubicin in Japanese Patients With Malignant Lymphoma: Relationship With Leukocytopenia and Neutropenia

Abstract

To clarify the pharmacokinetic properties of idarubicin (IDA) in Japanese patients and to clarify the relationship between the pharmacokinetic parameters of IDA or idarubicinol (IDAol), an active metabolite of IDA, and leukocytopenia or neutropenia, we examined the pharmacokinetics of IDA in patients 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/m2) was administered by intravenous infusion for 5 minutes. The elimination half lives (t 1/2) of IDA were 11.0 hours and 12.5 hours after administration of 12 and 15 mg/m2 IDA, respectively. IDAol appeared rapidly both in plasma and in blood cells, and its concentrations exceeded those of IDA within 4 hours. IDAol had a very long t 1/2 (69.2 hours and 70.0 hours for 12 and 15 mg/m2, respectively). The areas under the concentration curves of IDAol in plasma were 3.4 and 5.8 times higher than those of IDA after 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 steady-state volume of distribution of IDA in plasma and in blood cells correlated significantly with the nadirs of white blood cells and neutrophils. These results suggest that both IDA and IDAol play an important role in leukocytopenia or neutropenia. No substantial differences between Japanese and Caucasian people in the pharmacokinetics of IDA were apparent.

Improved stability of lipiodol–drug emulsion for transarterial chemoembolisation of hepatocellular carcinoma results in improved pharmacokinetic profile: Proof of concept using idarubicin

“…Immediately after injection of the emulsion, we did not detect any idarubicin in the plasma; it took at least a few minutes for the drug to appear. When compared with data in the literature, our findings highlighted the improved PK profile of idarubicin c-TACE compared with both doxorubicin c-TACE (mean C max 10 times lower [7]) and idarubicin IV injection (mean AUC 0-24h three times lower [33]), and also showed that the in vivo release of idarubicin from a lipiodol-based emulsion was very close to that observed from DEEs [23,34] (Table 4). The first peak of idarubicinol concentration between 5 and 10 min after injection of the emulsion can be explained by the very quick extraction of part of the idarubicin by hepatocytes followed by its immediate metabolisation.…”