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 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.
Fukushima
T
T
Internal Medicine, National Kanazawa Hospital, Kanazawa, Japan. fukus@kinbyou.hosp.go.jp
Yamashita
T
T
Goto
N
N
Ueda
T
T
Okabe
K I
KI
Kuraishi
Y
Y
Ohno
R
R
Urabe
A
A
Ogawa
M
M
D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001711:Biotransformation; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D006801:Humans; D015255:Idarubicin / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D007564:Japan; D007958:Leukocyte Count; D007970:Leukopenia / Q000139:chemically induced*; D008223:Lymphoma / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced*
D000903:Antibiotics, Antineoplastic; C054440:idarubicinol; D015255:Idarubicin; D003630:Daunorubicin