Daunorubicinの白血病患者における体内動態
書誌事項
- タイトル別名
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- Pharmacokinetic study of daunorubicin in patients with leukemia.
抄録
Daunorubicin (DNR) is one of the most important chemotherapeutic agents used in the treatment of patients with leukemia. In order to elucidate the pharmacodynamics of DNR administrated into patients with leukemia, 40mg of DNR was administered intravenously for 3 minutes into the patients with leukemia in the course of combination chemotherapy. Concentration of DNR in plasma, red blood cells and urine was measured by high-performance liquid chromatography (HPLC). A three-compartment-open-body model was applied to kinetic study of the blood concentration of DNR. The results from ten patients with leukemia are concluded as follows.<BR>1. Peak level of DNR concentration was 228.00±204.00ng/ml in plasma and 237.00±111.00ng/g in red blood cells, both of which were revealed five minutes after the injection. Blood concentration curve was composed of α, β and γ phase. Half-life of α, β and γ phase was 0.0351± 0.0157 hr (almost 2 minutes), 1.82± 2.01 hr and 15.8 ± 8.4 hr, respectively.<BR>2. Daunorubicinol (DNR-OL) was proved to be a main metabolite of DNR. The peak level of DNR-OL was 96.50± 62.90ng/ml in plasma and 205.00 ± 115.00ng/g in red blood cells, both of which reached five minutes after injection. It was found two hours after DNR injection that the concentration of DNR was 20.00 ± 15.80ng/ml in plasma and 40.00± 19.5ng/g in red blood cells and that DNR-OL concentration was 41.40 ± 27.20ng/ml in plasma and 40.20± 13.60ng/g in red blood cells. Thus DNR-OL concentration was revealed to be higher than that of DNR two hours after the injection.<BR>3. Pharmacokinetic study using three-compartment-open-body model revealed that intercompartmental distribution rate constant for circulating compartment to tissue compartment II (K12) and tissue compartment III (K13) were greater than that for tissue compartment II and III to circulating compartment (K21, K31). Pharmacokinetic study also revealed that the distribution volume of circulating compartment (V1) was smaller than that of tissue compartment (V2+V3). These results support that DNR injected intravenously in a bolus dose transfers to tissue quickly, and is sustained in tissue at higher concentration and released from tissue very slowly.<BR>4. Percent excretion of DNR into urine was 6.33 ± 2.93% for DNR and 5.30± 2.48% for DNR-OL within 24 hours after the injection respectively. The cumulative percent excretion of DNR and metabolites into urine was only 11.8± 5.1% at 24 hours after the injection. This result shows that the part of DNR which is excreted into urine within 24 hours after the injection is very small.
収録刊行物
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- CHEMOTHERAPY
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CHEMOTHERAPY 35 (5), 398-410, 1987
公益社団法人 日本化学療法学会
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詳細情報 詳細情報について
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- CRID
- 1390282681255556992
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- NII論文ID
- 130004195609
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- ISSN
- 18845894
- 00093165
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- 本文言語コード
- ja
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- データソース種別
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- JaLC
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可