Tornatore Kathleen M, Gilliland-Johnson Kristin K, Farooqui Mahfooz, Reed Kris A, Venuto Rocco C
Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, 319 Cooke Hall, Buffalo, NY 14260-1200, USA.
J Clin Pharmacol. 2004 Sep;44(9):1003-11. doi: 10.1177/0091270004268130.
Chronic glucocorticoid therapy is prescribed in renal transplant recipients according to empiric dose-tapering schedules, which assume a similar pharmacologic response in men and women. The study objectives were (a) to compare the pharmacokinetics of methylprednisolone in premenopausal renal transplant recipients with previously studied male counterparts and (b) to describe the pharmacodynamic response of the hypothalamic-pituitary-adrenal axis during chronic steroid therapy. Thirteen stable premenopausal subjects (ages 30 to </=49 years) receiving chronic glucocorticoid therapy were evaluated for methylprednisolone, cortisol, and adrenocorticotropin hormone (ACTH) over 24 hours after an intravenous infusion of methylprednisolone sodium succinate. Most patients were evaluated during the luteal phase of the menstrual cycle. Pharmacokinetic parameters of methylprednisolone with cortisol and ACTH responses were determined. Results were compared to counterpart male subjects who participated in a prior study. The total clearance of methylprednisolone for the female subjects was 15.6 +/- 5.99 L/h compared to the males with 21.5 +/- 8.67 L/h (P <.05). When normalized for total or lean body weight, no significant difference was noted (P =.614). A 3-fold interpatient variation in weight-adjusted clearance was noted for female subjects. Dose-normalized methylprednisolone a AUC was greater in women (66.1 +/- 19.8 ngh/mL) than men (46.4 +/- 19.7 ngh/mL) (P =.174). Total cortisol AUC was not different between groups (P =.599). Despite chronic steroid therapy, 9 of 13 women had a normal cortisol profile and an ACTH AUC of 299 +/- 102 pg*h/mL. It was concluded that methylprednisolone clearance in women was significantly slower compared to men. When drug clearance was normalized for total and lean body weight, no gender difference was noted. These findings are in contrast to prior data indicating a more rapid methylprednisolone clearance in healthy women. These findings suggest that doses of glucocorticoids should be prescribed on a milligram/kilogram basis instead of empiric dosing schedules.
肾移植受者的慢性糖皮质激素治疗是根据经验性的剂量递减方案进行的，该方案假定男性和女性的药理反应相似。本研究的目的是：（a）比较绝经前肾移植受者与先前研究的男性受者中甲基强的松龙的药代动力学；（b）描述慢性类固醇治疗期间下丘脑-垂体-肾上腺轴的药效学反应。在静脉输注甲泼尼龙琥珀酸钠后24小时内，对13名接受慢性糖皮质激素治疗的稳定绝经前受试者（年龄30至≤49岁）的甲泼尼龙、皮质醇和促肾上腺皮质激素（ACTH）进行了评估。大多数患者在月经周期的黄体期接受评估。测定了甲泼尼龙的药代动力学参数以及皮质醇和ACTH的反应。将结果与参与先前研究的男性受试者进行比较。女性受试者甲泼尼龙的总清除率为15.6±5.99L/h，而男性为21.5±8.67L/h（P<.05）。按总体重或瘦体重进行标准化后，未发现显著差异（P=.614）。女性受试者的体重调整清除率存在3倍的患者间差异。女性的剂量标准化甲泼尼龙AUC（66.1±19.8ngh/mL）高于男性（46.4±19.7ngh/mL）（P=.174）。两组之间的总皮质醇AUC无差异（P=.599）。尽管进行了慢性类固醇治疗，但13名女性中有9名的皮质醇水平正常，ACTH AUC为299±102pg*h/mL。得出的结论是，与男性相比，女性中甲泼尼龙的清除明显较慢。当按总体重和瘦体重对药物清除进行标准化时，未发现性别差异。这些发现与先前的数据相反，先前数据表明健康女性中甲泼尼龙的清除更快。这些发现表明，糖皮质激素的剂量应按毫克/千克来开具，而不是采用经验性给药方案。
