Dextran-methylprednisolone succinate as a prodrug of methylprednisolone: plasma and tissue disposition.
Dextran-methylprednisolone succinate as a prodrug of methylprednisolone: plasma and tissue disposition.
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右旋糖酐-甲基泼尼松龙琥珀酸酯作为甲基泼尼松龙的前药：血浆和组织处置。
DOI：
10.1002/jps.1158
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发表时间：
2001
影响因子：
3.8
通讯作者：
Mehvar,R
中科院分区：
文献类型：
--
作者：
Zhang,X;Mehvar,R
研究了甲基强的松龙（MP）的大分子前体药物葡聚糖（70 kDa）-琥珀酸甲基强的松龙（MP）在大鼠体内的血浆和组织分布。向不同组大鼠（n= 4/组/时间点）的尾静脉单次给予5 mg/kg剂量的β-内酰胺酶或未结合MP。在注射顺铂（0-96 h）或MP（0-2 h）后的不同时间采集血液（心脏穿刺）和组织（肝、脾、肾、心脏、肺、胸腺和脑）。分别通过尺寸排阻色谱法（SEC）和反相高效液相色谱法（HPLC）分析样品中的NTA和MP浓度。MP与70 kDa葡聚糖结合导致类固醇的稳态分布容积、清除率和终末血浆速率常数分别降低22、300和30倍。至于组织分布，结合物主要将类固醇递送至脾脏和肝脏，如类固醇的组织/血浆曲线下面积（AUC）比分别增加19倍和3倍所示。另一方面，前药在其他器官中的组织/血浆AUC比可忽略不计。活性MP在脾脏和肝脏中缓慢从顺铂释放，这些组织中再生MP的AUC分别是母体药物给药后的55倍和4.8倍。相比之下，在注射β-内酰胺酶的大鼠血浆中未检测到母体药物。这些结果表明，甲基强的松龙可能是有用的MP的靶向输送到脾脏和肝脏中的活性药物缓慢释放。© 2001 Wiley利斯公司和American Pharmaceutical Association J Pharm Sci 90：2078-2087，2001
Plasma and tissue disposition of a macromolecular prodrug of methylprednisolone (MP), dextran (70 kDa)–methylprednisolone succinate (DMP), was studied in rats. Single 5‐mg/kg doses of DMP or unconjugated MP were administered into the tail veins of different groups of rats (n= 4/group/time point). Blood (cardiac puncture) and tissues (liver, spleen, kidney, heart, lung, thymus, and brain) were collected at various times after DMP (0–96 h) or MP (0–2 h) injections. Concentrations of DMP and MP in samples were analyzed by size‐exclusion chromatography (SEC) and reversed‐phase high‐performance liquid chromatography (HPLC), respectively. Conjugation of MP with 70‐kDa dextran resulted in 22‐, 300‐, and 30‐fold decreases in the steady‐state volume of distribution, clearance, and terminal plasma rate constant of the steroid, respectively. As for tissue distribution, the conjugate delivered the steroid primarily to the spleen and liver as indicated by 19‐ and 3‐fold increases, respectively, in the tissue/plasma area under the curve (AUC) ratios of the steroid. On the other hand, the tissue/plasma AUC ratios of the prodrug in other organs were negligible. Active MP was released from DMP slowly in the spleen and liver, and AUCs of the regenerated MP in these tissues were 55‐ and 4.8‐fold, respectively, higher than those after the administration of the parent drug. In contrast, no parent drug was detected in the plasma of DMP‐injected rats. These results indicate that DMP may be useful for the targeted delivery of MP to the spleen and liver where the active drug is slowly released. © 2001 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:2078–2087, 2001
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影响因子：
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