PHARMACOKINETICS OF THE ANTIVIRAL AGENT 3-DEAZANEPLANOCIN-A
PHARMACOKINETICS OF THE ANTIVIRAL AGENT 3-DEAZANEPLANOCIN-A
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DOI：
10.1007/bf03189670
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发表时间：
1995-07-01
影响因子：
1.9
通讯作者：
HUGGINS, JW
中科院分区：
文献类型：
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作者：
COULOMBE, RA;SHARMA, RP;HUGGINS, JW
研究了新型抗病毒药物3-去氮普兰诺星A（c（3）Nep）在雌性BALB/c小鼠体内的药代动力学。动物单次静脉注射[H-3]-c（3）Nep（0.1 mg/kg：10 μ Ci），然后在不同时间间隔收集血液和选定组织，持续72 h。c（3）Nep的血药浓度-时间数据最好用一级消除的二室开放模型近似。消除半衰期为12.8 min，曲线下面积（AUC）为3.38 mu g.min.ml（-1）。c（3）Nep在组织中的分布不广泛。在给药后30、120分钟和24小时，肾脏和肝脏含有最高量的药物，但该量不超过1 μ g/g组织。在这些时间段，组织中的大部分活性代表c（3）Nep的标记衍生物，表明该化合物转化为稳定的代谢产物。血液中标记的转化产物的存在证实了该药物在体内代谢。c（3）Nep在体外与血浆蛋白结合的事实可以解释这种药物有限的组织分布。c（3）Nep的半衰期和组织分布与碳环3-脱氮腺苷、腺苷核苷类抗病毒药物和同型半胱氨酸水解酶抑制剂不同。
The pharmacokinetics of 3-deazaneplanocin A (c(3)Nep), a competitive inhibitor of S-adenosyl-L-homocysteine (AdoHcy) hydrolase and novel antiviral agent, was investigated in female BALB/c mice. Animals were given a single intravenous dose of [H-3]-c(3)Nep (0.1 mg/kg: 10 mu Ci), and blood and selected tissues were collected at various intervals thereafter for up to 72 h. The plasma concentration versus time data for c(3)Nep was best approximated by a two-compartment open model with first order elimination. The elimination half-life was 12.8 min, the area-under curve (AUG) was 3.38 mu g.min.ml(-1). The distribution of c(3)Nep into tissues was not extensive. Following 30, 120 min,and 24 h after dosing, the kidneys and the liver contained the highest amount of drug, but this amount did not exceed 1 mu g/g tissue. At these time periods, the majority of activity in the tissues represented labeled derivatives of c(3)Nep indicating that this compound was converted to stable metabolites. The presence of labeled conversion products in the blood confirmed that this drug is metabolized in vivo. The fact that c(3)Nep bound to plasma proteins in vitro may explain this drug's limited tissue distribution. The half-life anti tissue distribution of c(3)Nep were different from those of carbocyclic 3-deazaadenosine, a related adenosine nucleoside antiviral drug and AdoHcy hydrolase inhibitor.