Pharmacokinetics of S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro- 3-trifluoromethyl-phenyl)-propionamide in rats, a non-steroidal selective androgen receptor modulator.
Pharmacokinetics of S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro- 3-trifluoromethyl-phenyl)-propionamide in rats, a non-steroidal selective androgen receptor modulator.
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非甾体选择性雄激素受体调节剂 S-3-(4-乙酰氨基-苯氧基)-2-羟基-2-甲基-N-(4-硝基-3-三氟甲基-苯基)-丙酰胺在大鼠体内的药代动力学。
DOI：
10.1080/0049825041008962
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Dalton,JT
中科院分区：
文献类型：
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作者：
Kearbey,JD;Wu,D;Gao,W;Miller,DD;Dalton,JT
1.S-3-（4-乙酰氨基-苯氧基）-2-羟基-2-甲基-N-（4-硝基-3-三氟甲基-苯基）-丙酰胺（也称为S-4）是一种非甾体选择性雄激素受体调节剂，具有组织选择性雄激素和合成代谢作用。本研究的目的是检查S-4在大鼠中的全身药代动力学、消除和经口生物利用度。2.将35只体重约250 g的雄性Sprague-Dawley大鼠随机分配至7个给药组之一。 通过颈静脉导管给予0.5、1、10和30 mg kg− 1静脉给药。经口灌胃给予1、10和30 mg/kg。使用经验证的高效液相色谱法或高效液相色谱/质谱法测定血浆浓度。3.清除率范围为1.0 - 2.1 ml min− 1 kg − 1，并随剂量而变化。 所有给药组的分布容积约为0.448 l kg− 1。口服生物利用度也具有剂量依赖性，较低剂量显示完全口服生物利用度。在试验剂量范围内，S-4的半衰期为2.6 - 5.3 h。4.研究表明，S-4在大鼠中吸收迅速，清除缓慢，分布容积中等。 S-4的药代动力学和口服生物利用度表明，它是临床开发的优秀候选药物。
1.S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide (also known as S-4) is a non-steroidal selective androgen receptor modulator demonstrating tissue-selective androgenic and anabolic effects. The purpose of the present study was to examine the systemic pharmacokinetics, elimination and oral bioavailability of S-4 in rats.2. Thirty-five male Sprague–Dawley rats weighing approximately 250 g were randomly assigned to one of seven treatment groups. Intravenous doses of 0.5, 1, 10, and 30 mg kg−1were given via a jugular catheter. Oral doses of 1, 10 and 30 mg kg−1were administered via gavage. Plasma concentrations were determined using a validated high-performance liquid chromatography or by a high-performance liquid chromatography/mass spectrometry method.3. Clearances ranged between 1.0 and 2.1 ml min−1kg−1and varied with dose. The volume of distribution was approximately 0.448 l kg−1in all treatment groups. Oral bioavailability was also dose dependent, with the lower doses showing complete oral bioavailability. The half-life of S-4 over the dose range tested was between 2.6 and 5.3 h.4. It was demonstrated that S-4 is rapidly absorbed, slowly cleared, and has a moderate volume of distribution in rats. The pharmacokinetics and oral bioavailability of S-4 indicate that it is an excellent candidate for clinical development.