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首页> 外文期刊>Chemotherapy: International Journal of Experimental and Clinical Chemotherapy >Pharmacokinetic profile of the anti-sickling hydroxyurea in wild-type and transgenic sickle cell mice.
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Pharmacokinetic profile of the anti-sickling hydroxyurea in wild-type and transgenic sickle cell mice.

机译：抗镰状羟基脲在野生型和转基因镰状细胞小鼠中的药代动力学概况。

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摘要

The pharmacokinetic profile of hydroxyurea (HU) was investigated by measuring the rate of drug disappearance from the plasma in wild-type and transgenic (Tg) sickle cell mice. The absorption and elimination processes of HU exhibited first-order kinetics after intraperitoneal administration of HU at 10, 50, 100 or 200 mg/kg body weight (BW). The dosage had a marked effect on the pharmacokinetics of HU in the Tg sickle cell mice. Although the area under the plasma concentration curve (AUC) increased in direct proportion with the HU dose in the wild-type mice, the AUC increased to a much greater extent at higher doses in the Tg sickle cell mice. In the Tg sickle cell mice, there was a considerable increase in the mean residence time (MRT) and a significant reduction in the apparent clearance (CL/F) at HU dose > or =100 mg/kg BW, when compared to the lower doses. At an HU dose of 200 mg/kg BW, the CL/F in the Tg sickle cell mice was reduced by about 50% of the value obtained at a dose of 10 mg/kg BW. This phenomenon was not noticeable in the wild-type mice. The MRT value in the wild-type mice at all doses was relatively constant. The steady-state distribution volume of HU in both the wild-type and Tg sickle cell mice was relatively constant at all doses of the drug. The AUC, CL/F, MRT, and terminal half-life values at any given HU dose showed significant differences between the wild-type and Tg sickle cell mice. Following intraperitoneal administration of HU at a dose of 10, 50, 100, or 200 mg/kg BW, the mean percentage of HU excreted in the urine of the wild-type and Tg sickle cell mice over 120 min was 84 +/- 6.4% and 50 +/- 8.2%, respectively, indicating a significant difference in the amount of HU excreted in urine in the two kinds of mice. The results obtained in this study may be useful in establishing an optimal dose of HU in the treatment and management of patients with sickle cell disease and other hemoglobinopathies.
机译：通过测量野生型和转基因（Tg）镰刀细胞小鼠血浆中药物消失的速率，研究了羟基脲（HU）的药代动力学特征。腹膜内给予10、50、100或200 mg / kg体重（BW）的HU后，HU的吸收和消除过程表现出一级动力学。该剂量对Tg镰状细胞小鼠中HU的药代动力学具有显着影响。尽管在野生型小鼠中血浆浓度曲线（AUC）下的面积与HU剂量成正比增加，但在更高剂量的Tg镰状细胞小鼠中，AUC的增加幅度更大。在Tg镰状细胞小鼠中，当HU剂量大于或等于100 mg / kg BW时，平均停留时间（MRT）显着增加，并且表观清除率（CL / F）显着降低，而剂量。在200 mg / kg BW的HU剂量下，Tg镰状细胞小鼠的CL / F降低了10 mg / kg BW剂量下的CL / F。这种现象在野生型小鼠中并不明显。在所有剂量的野生型小鼠中的MRT值相对恒定。在所有剂量的药物中，野生型和Tg镰状细胞小鼠中HU的稳态分布体积均相对恒定。在任何给定的HU剂量下，AUC，CL / F，MRT和终末半衰期值在野生型和Tg镰状细胞小鼠之间均显示出显着差异。腹膜内给予HU剂量为10、50、100或200 mg / kg BW后，在120分钟内，野生型和Tg镰状细胞小鼠尿液中HU的平均排泄率为84 +/- 6.4 ％和50 +/- 8.2％，分别表明在两种小鼠尿中排出的HU量有显着差异。这项研究中获得的结果可能有助于确定治疗和治疗镰状细胞病和其他血红蛋白病患者的最佳HU剂量。

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