Ebling W F, Szefler S J, Jusko W J
Drug Metab Dispos. 1985 May-Jun;13(3):296-304.
Methodology was evolved for comparison of methylprednisolone disposition in man and rabbit. Methylprednisolone, methylprednisone, and methylprednisolone hemisuccinate ester concentrations in plasma were measured by HPLC methodology after iv administration of each compound to rabbits. Methylprednisolone hemisuccinate is rapidly and completely hydrolyzed to methylprednisolone with a half-life of 10 min. Dosing with the free alcohol or ester produces identical disposition curves for methylprednisolone. Methylprednisolone was found to undergo rapid and reversible metabolism with methylprednisone, a phenomenon also seen in man. Plasma concentrations of methylprednisolone are appreciably greater than the metabolite regardless of the form of steroid given. Administration of the metabolite yields 67% availability of methylprednisolone. The occurrence of reversible metabolism produces an apparent clearance which is about 71% of the value of the "real" elimination clearance for both steroids. Man and rabbit show identical plasma protein binding of methylprednisolone (77%). Small differences in apparent clearance (man, 5.74 ml/min/kg; rabbit, 7.93 ml/min/kg) can be accounted for by the animal scale-up principle (body weight0.89). The rabbit is thus a useful animal model for further assessing mechanisms of drug- or disease-steroid interactions which occur in man.
已开发出用于比较甲基强的松龙在人和兔体内处置情况的方法。给兔静脉注射每种化合物后，通过高效液相色谱法测定血浆中甲基强的松龙、甲基强的松和甲基强的松龙半琥珀酸酯的浓度。甲基强的松龙半琥珀酸酯迅速且完全水解为甲基强的松龙，半衰期为10分钟。给予游离醇或酯后，甲基强的松龙的处置曲线相同。发现甲基强的松龙与甲基强的松发生快速且可逆的代谢，这一现象在人体中也可见。无论给予何种形式的类固醇，甲基强的松龙的血浆浓度均明显高于代谢物。给予代谢物后，甲基强的松龙的可用性为67%。可逆代谢的发生产生了一个表观清除率，该清除率约为两种类固醇“真正”消除清除率值的71%。人和兔体内甲基强的松龙的血浆蛋白结合率相同（77%）。表观清除率的微小差异（人，5.74毫升/分钟/千克；兔，7.93毫升/分钟/千克）可以通过动物放大原则（体重0.89）来解释。因此，兔是进一步评估人体中发生的药物或疾病与类固醇相互作用机制的有用动物模型。
