Enever R P, Fotherby K, Naderi S, Lewis G A
Steroids. 1983 Mar;41(3):381-96. doi: 10.1016/0039-128x(83)90109-5.
Four 17 beta-esters of norethisterone (17 alpha-ethynyl-17 beta-hydroxyestr-4-en-3-one), formulated both as oily solutions and aqueous suspensions, were administered intramuscularly to rabbits and free plasma levels measured for periods up to 9 weeks. For all formulations of the compounds, the disappearance of norethisterone following peak plasma levels obeyed first-order kinetics. Since different slope values were obtained for different formulations of the same compound, the values reflected the release rates of the esters from the formulations. Fusion data, partition coefficients and solubilities of the compounds in 2,2,4-trimethylpentane and water were obtained and these properties were related to the biological activity of the formulations. For oily solutions, the differences in plasma levels were ascribed to the different partition coefficients of the esters between the oil and tissue fluids. For suspensions, the different activity in relation to an oily solution of an ester was related to the strength of intermolecular forces in the crystal lattice and to the relative thermodynamic activity in the two formulations. The results demonstrate that microcrystalline suspensions do not always have a longer duration of activity than oily solutions of the same compound after intramuscular injection.
将炔诺酮（17α-乙炔基-17β-羟基雌甾-4-烯-3-酮）的四种17β-酯制成油溶液和水悬浮液，肌肉注射给兔子，并测定长达9周的游离血浆水平。对于化合物的所有制剂，血浆峰值水平后炔诺酮的消失符合一级动力学。由于同一化合物的不同制剂获得了不同的斜率值，这些值反映了酯从制剂中的释放速率。获得了化合物在2,2,4-三甲基戊烷和水中的融合数据、分配系数和溶解度，这些性质与制剂的生物活性相关。对于油溶液，血浆水平的差异归因于酯在油和组织液之间的不同分配系数。对于悬浮液，与酯的油溶液相比，不同的活性与晶格中的分子间力强度以及两种制剂中的相对热力学活性有关。结果表明，肌肉注射后，微晶悬浮液的活性持续时间并不总是比同一化合物的油溶液长。
