Antitumor Activity and Pharmacology of 1‐β‐D‐Arabinofuranosylcytosine‐5′‐stearylphosphate: An Orally Active Derivative of 1‐β‐D‐Arabinofuranosylcytosine
Antitumor Activity and Pharmacology of 1‐β‐D‐Arabinofuranosylcytosine‐5′‐stearylphosphate: An Orally Active Derivative of 1‐β‐D‐Arabinofuranosylcytosine
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1-β-D-阿拉伯呋喃糖基胞嘧啶-5′-硬脂基磷酸酯的抗肿瘤活性和药理学：1-β-D-阿拉伯呋喃糖基胞嘧啶的口服活性衍生物
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发表时间：
1989
期刊：
影响因子：
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通讯作者：
M. Saneyoshi
中科院分区：
文献类型：
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作者：
K. Kodama;M. Morozumi;K. Saitoh;A. Kuninaka;H. Yoshino;M. Saneyoshi
经口给药1-β-D-阿拉伯呋喃糖基胞嘧啶-5 ′-烷基磷酸酯（CnPCA）对小鼠L1210白血病具有抗肿瘤活性。发现CnPCA的磷酸部分上的烷基的最佳长度为十四烷基（C14）和二十三烷基（C23）之间，以表现出高的抗肿瘤活性。发现该系统中最具活性的烷基衍生物是l-β-D-阿拉伯呋喃糖基胞嘧啶-5 ′-硬脂酰磷酸（C18 PCA）。C18 PCA的最佳和最小有效剂量分别为100和6，25 mg/kg/d（q1 d，第1天至第5天）。C18 PCA的最大T/C%约为220。C18 PCA的抗肿瘤活性与给药方案和给药途径无明显依赖性。经口给予100 mgAg（170 μmol/kg）C18 PCA后，1-β-D-阿拉伯呋喃糖基胞嘧啶（ara-C）的血浆浓度保持在0.4 - 0.75 μmol/ml范围内24 h。这些结果表明，口服C18 PCA可通过胃肠道完整吸收，并且ara-C会长时间释放。C18 PCA被认为是ara-C的口服活性贮库形式
The antitumor activity of l‐β‐D‐arabinofuranosylcytosine‐5′‐alkylphosphates (CnPCAs) against L1210 leukemia in mice after oral administration was demonstrated. The optimum length of the alkyl group on the phosphate moiety of CnPCA for exhibiting a high antitumor activity was found to be between tetradecyl (C14) and tricosyl (C23). The most active alkyl derivative in this system was found to be l‐β‐D‐arabinofuranosylcytosine‐5′‐stearylphosphate (C18PCA). The optimum and minimum effective doses of C18PCA were 100 and 6,25 mg/kg/day (q1d, day 1 to day 5), respectively. The maximum T/C% of C18PCA was approximately 220. The antitumor activity of C18PCA was not greatly dependent on the treatment schedule and route. Plasma concentration of 1‐β‐D‐arabinofurano‐sylcytosine (ara‐C) remained in the range of 0.4 to 0.75 μmol/ml for 24 h after oral administration of 100 mgAg (170 μmol/kg) of C18PCA. These results indicate that C18PCA administered per orally is absorbed intact through the gastrointestinal tract and ara‐C is released for a long period of time. C18PCA is regarded as an orally active depot form of ara‐C