Toutain P L, Koritz G D, Fayolle P M, Alvinerie M
J Pharm Sci. 1986 Mar;75(3):251-5. doi: 10.1002/jps.2600750309.
The absolute bioavailability and pharmacokinetic parameters of two methylprednisolone formulations (methylprednisolone sodium succinate and methylprednisolone acetate) were determined in five dogs. Plasma concentrations of methylprednisolone, methylprednisolone sodium succinate, and methylprednisolone acetate were measured by sensitive and specific high-performance liquid chromatographic methods. After intravenous methylprednisolone sodium succinate administration, methylprednisolone was released rapidly but the extent of availability was rather low (43.6%). This has been tentatively explained in terms of its subsequent single-pass metabolism in the liver, i.e., hepatic hydrolysis of methylprednisolone sodium succinate followed by immediate hepatic elimination of the released methylprednisolone. After intramuscular administration of methylprednisolone acetate, its absorption was slow (half-time of absorption, 69.04 h) and the availability of the released methylprednisolone was low (42.7%). Therapeutic implications of these results are discussed, especially those which are relevant to shock therapy.
在五只犬中测定了两种甲泼尼龙制剂（甲泼尼龙琥珀酸钠和甲泼尼龙醋酸酯）的绝对生物利用度和药代动力学参数。采用灵敏且特异的高效液相色谱法测定血浆中甲泼尼龙、甲泼尼龙琥珀酸钠和甲泼尼龙醋酸酯的浓度。静脉注射甲泼尼龙琥珀酸钠后，甲泼尼龙迅速释放，但可利用程度相当低（43.6%）。这初步解释为其随后在肝脏中的单次通过代谢，即甲泼尼龙琥珀酸钠在肝脏水解，随后释放的甲泼尼龙立即被肝脏清除。肌肉注射甲泼尼龙醋酸酯后，其吸收缓慢（吸收半衰期为69.04小时），释放的甲泼尼龙的可利用性较低（42.7%）。讨论了这些结果的治疗意义，特别是与休克治疗相关的意义。
