Sarna S, Hoppu K, Neuvonen P J, Laine J, Holmberg C
Children's Hospital, University of Helsinki, Finland.
J Clin Endocrinol Metab. 1997 Jan;82(1):75-7. doi: 10.1210/jcem.82.1.3639.
Some patients receiving glucocorticoids develop adverse effects even with very low doses, whereas others fail to achieve the desired effects with the usual therapeutic doses. We hypothesized that glucocorticoid exposure, rather than the dose, would predict the development of adverse effects in children receiving long-term glucocorticoid treatment. Sixteen liver and 10 renal transplant recipients on triple immunosuppression were studied. Serum total methylprednisolone (MP) and cortisol were determined before and up to 10 h after peroral MP administration. Heights were recorded 6 months before and after the study day. The MP dose (in milligrams per kilogram) was not correlated with the serum cortisol concentration or with the change in height SD score. The area under the serum MP time vs. concentration curve was inversely related to the serum cortisol concentration and to the height SD score, and was the best predictor of both adrenal function and growth. Dosing according to area under the serum MP time vs. concentration curve in children receiving long-term glucocorticoid treatment may substantially reduce the incidence of adverse effects without affecting therapeutic efficacy.
一些接受糖皮质激素治疗的患者即使使用非常低的剂量也会出现不良反应,而另一些患者使用常规治疗剂量却未能达到预期效果。我们推测,对于接受长期糖皮质激素治疗的儿童,糖皮质激素的暴露量而非剂量能预测不良反应的发生。对16例接受三联免疫抑制治疗的肝移植受者和10例肾移植受者进行了研究。在口服甲泼尼龙(MP)之前及之后长达10小时测定血清总甲泼尼龙(MP)和皮质醇。记录研究日前后6个月的身高。MP剂量(毫克/千克)与血清皮质醇浓度或身高标准差评分的变化无关。血清MP时间-浓度曲线下面积与血清皮质醇浓度和身高标准差评分呈负相关,并且是肾上腺功能和生长的最佳预测指标。在接受长期糖皮质激素治疗的儿童中,根据血清MP时间-浓度曲线下面积给药可能会在不影响治疗效果的情况下大幅降低不良反应的发生率。