Glynn A M, Slaughter R L, Brass C, D'Ambrosio R, Jusko W J
Clin Pharmacol Ther. 1986 Jun;39(6):654-9. doi: 10.1038/clpt.1986.114.
The disposition of methylprednisolone was examined in six normal subjects after the injection of 20 mg iv methylprednisolone sodium succinate. Disposition studies were performed both without and with ketoconazole, 200 mg/day, for 6 days. Ketoconazole increased the methylprednisolone AUC and mean residence time (by 135% and 66%, respectively) and decreased clearance (60%), the terminal phase slope, and the volume of distribution. These findings are typical of macrolide antibiotic alteration of methylprednisolone disposition and consistent with reports of inhibition of drug metabolism by ketoconazole. Methylprednisolone reduced the 24-hour cortisol AUC by 44%, but morning cortisol concentrations returned to normal. Ketoconazole with methylprednisolone further reduced the 24-hour cortisol AUC and suppressed morning cortisol concentrations. Thus ketoconazole inhibits methylprednisolone disposition and extends the adrenal suppression effects of this corticosteroid.
对6名正常受试者静脉注射20mg甲泼尼龙琥珀酸钠后，研究了甲泼尼龙的处置情况。在未使用酮康唑以及使用酮康唑（200mg/天，共6天）的情况下均进行了处置研究。酮康唑使甲泼尼龙的AUC和平均驻留时间分别增加了135%和66%，并使清除率降低了60%，同时降低了终末相斜率和分布容积。这些发现是大环内酯类抗生素改变甲泼尼龙处置情况的典型表现，与酮康唑抑制药物代谢的报道一致。甲泼尼龙使24小时皮质醇AUC降低了44%，但早晨皮质醇浓度恢复正常。酮康唑与甲泼尼龙联合使用进一步降低了24小时皮质醇AUC，并抑制了早晨皮质醇浓度。因此，酮康唑抑制甲泼尼龙的处置，并延长了这种皮质类固醇的肾上腺抑制作用。
