Testosterone 17β-N,N-dimethylglycinate hydrochloride:: A prodrug with a potential for nasal delivery of testosterone
Testosterone 17β-N,N-dimethylglycinate hydrochloride:: A prodrug with a potential for nasal delivery of testosterone
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DOI：
10.1002/jps.10083
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发表时间：
2002-03-01
影响因子：
3.8
通讯作者：
Hussain, MA
中科院分区：
文献类型：
--
作者：
Hussain, AA;Al-Bayatti, AA;Hussain, MA
本研究的目的是检查使用水溶性前体药物TS 17 β-N，N-二甲基甘氨酸盐酸盐经鼻途径全身递送难溶性药物睾酮（TS）的潜力。在大鼠中进行了前药的理化性质、在人肝匀浆中的体外水解以及体内鼻内和静脉内实验。前药的水溶解度大于100 mg/mL，而TS为0.01 mg/mL，其在0.05 M磷酸盐缓冲液（pH 6）和辛醇之间的对数分配系数为2.4。发现前药在33%人肝匀浆中产生TS，并从鼻腔中快速定量吸收。鼻内给药后前药和TS的生物利用度与同等剂量静脉给药后相似。这些大鼠研究表明，TS的这种水溶性前药可能对TS缺乏症的治疗具有治疗作用。(C)2002 Wiley-Liss，Inc.
The purpose of this study was to examine the potential of the nasal route for the systemic delivery of the poorly water-soluble drug testosterone (TS) using a water-soluble prodrug, TS 17beta-N,N-dimethylglycinate hydrochloride. The physicochemical properties of the prodrug, in vitro hydrolysis in human liver homogenate, and in vivo nasal and intravenous experiments were performed in rats. The aqueous solubility of the prodrug was more than 100 mg/mL, compared with 0.01 mg/mL for TS, and its log partition coefficient between 0.05 M, phosphate buffer (pH 6) and octanol was 2.4. The prodrug was found to generate TS in 33% human liver homogenate and was absorbed from the nasal cavity rapidly and quantitatively. The bioavailabilities of both the prodrug and TS after nasal administration of the prodrug were similar to that after equivalent intravenous doses. These studies in rats suggest that this water-soluble prodrug of TS may have therapeutic utility for the management of TS deficiency. (C) 2002 Wiley-Liss, Inc.