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Duration of Suppression of Adrenal Steroids after Glucocorticoid Administration

机译:糖皮质激素给药后抑制肾上腺类固醇的持续时间

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Hydrocortisone has long been the treatment of choice for congenital adrenal hyperplasia (CAH). However, treatment with this medication remains problematic. Patients with 21-hydroxylase deficiency CAH have significant diurnal variation in the secretion of 17-hydroxyprogesterone (17OHP). When considering treatment strategies, this variation must be considered along with the pharmacokinetic and pharmacodynamic properties of exogenous glucocorticoids. Orally administered hydrocortisone is highly bioavailable, but it has a short time to maximum concentration (Tmax) and half life (T1/2). While prednisone has a somewhat longer Tmax and T1/2, they remain relatively short. There have been several studies of the pharmacodynamics of hydrocortisone. We present data indicating that the maximum effect of hydrocortisone in CAH patients is seen 3 hours after a morning dose. After an evening dose, suppression of adrenal hormones continues until approximately 0500 the next day. In both situations, however, there is a large degree of intersubject variability. These data are consistent with earlier published studies. Use of alternate specimen types, possibly in conjunction with delayed release hydrocortisone preparations under development, may allow the practitioner to design a medication regimen that provides improved control of androgen secretion. Whatever dosing strategy is used, clinical judgment is required to ensure the best outcome.
机译:长期以来,氢化可的松一直是先天性肾上腺皮质增生(CAH)的治疗选择。但是,用这种药物治疗仍然有问题。患有21-羟化酶缺乏症的CAH患者的17-羟孕酮(17OHP)分泌具有明显的昼夜变化。在考虑治疗策略时,必须考虑这种变化以及外源糖皮质激素的药代动力学和药效动力学特性。口服氢化可的松具有很高的生物利用度,但达到最大浓度(Tmax)和半衰期(T1 / 2)的时间很短。泼尼松的Tmax和T1 / 2稍长一些,但它们却相对较短。氢化可的松的药效学已有几项研究。我们提供的数据表明,在早上服用3小时后,氢化可的松在CAH患者中的最大作用。晚上服药后,肾上腺激素的抑制作用持续到第二天大约0500。但是,在两种情况下,主体间的差异都很大。这些数据与较早发表的研究一致。使用替代标本类型,可能与正在研发中的缓释氢化可的松制剂结合使用,可以使从业人员设计出能改善对雄激素分泌的控制的药物治疗方案。无论使用哪种给药策略,都需要临床判断以确保最佳结果。

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