Immediate versus modified release hydrocortisone in mitotane-treated patients with adrenocortical cancer.
Immediate versus modified release hydrocortisone in mitotane-treated patients with adrenocortical cancer.
复制标题
米托坦治疗的肾上腺皮质癌患者的速释氢化可的松与改良释放氢化可的松。
DOI：
10.1111/cen.13302
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发表时间：
2017
影响因子：
3.2
通讯作者：
Weigel M
中科院分区：
文献类型：
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作者：
Weigel M
氯米托坦诱导肝脏CYP 3A 4活性，导致皮质醇失活加速，并增加皮质醇结合球蛋白（CBG）。因此，在接受米托坦治疗的肾上腺皮质癌（ACC）患者中需要更高的氢化可的松剂量。改良释放氢化可的松尚未用于米托坦治疗的ACC患者。AimCase系列比较使用米托坦治疗的ACC患者的血清皮质醇，计算的游离血清皮质醇和ACTH水平立即和改良释放氢化可的松。设计立即和改良释放氢化可的松的药代动力学，每个剂量为40 - 20 - 0 mg，在9名ACC和辅助米托坦治疗的患者中。方法采用荧光酶免疫分析法测定10例继发性肾上腺皮质功能不全（SAI）患者血清皮质醇、血浆促肾上腺皮质激素（ACTH）水平，放射免疫分析法测定CBG水平。结果ACC患者服用40 mg速释氢化可的松后，血清游离皮质醇水平明显升高（46 ± 14 nmol/l）与SAI男性摄入10 mg速释氢化可的松后的水平（64 ± 16 nmol/l）或健康受试者的生理早晨游离皮质醇水平（31 ± 5 nmol/l）相似。与立即释放氢化可的松相比，ACC患者中40 mg修饰释放氢化可的松后的游离皮质醇水平显著降低（12 ± 3 nmol/l;P= 0·03）导致AUC普遍较低（98 ± 21 vs149 ± 37 nmol h/l; P= 0·02）。结论40 - 20 - 0 mg速释，但不是调释氢化可的松，在接受米托坦治疗的ACC患者中，米托坦治疗的患者应避免使用等效剂量的调释氢化可的松制剂。
ObjectiveMitotane induces hepatic CYP3A4 activity, resulting in accelerated cortisol inactivation, and also increases cortisol binding globulin (CBG). Therefore, higher hydrocortisone doses are required in patients with adrenocortical cancer (ACC) on mitotane treatment. Modified release hydrocortisone has not been used in mitotane‐treated ACC patients yet.AimCase series to compare serum cortisol, calculated free serum cortisol and ACTH levels in ACC patients on mitotane treatment with immediate and modified release hydrocortisone.DesignPharmacokinetics of immediate and modified release hydrocortisone, each administered at a dose of 40‐20‐0 mg, in nine patients with ACC and adjuvant mitotane treatment. For comparison, ten patients with secondary adrenal insufficiency (SAI) on three different hydrocortisone regimens and ten healthy males were included.MethodsSerum cortisol and plasma ACTH were measured by chemiluminescent enzyme immunoassay, and CBG by RIA, followed by calculation of free cortisol.ResultsCalculated free serum cortisol levels after 40 mg immediate release hydrocortisone in ACC patients (46 ± 14 nmol/l) were similar to those after 10 mg immediate release hydrocortisone intake in men with SAI (64 ± 16 nmol/l) or to the physiological morning free cortisol levels in healthy subjects (31 ± 5 nmol/l). Compared to immediate release hydrocortisone, free cortisol levels after 40 mg modified release hydrocortisone in ACC patients were significantly lower (12 ± 3 nmol/l;P= 0·03) resulting in a generally lower AUC (98 ± 21vs149 ± 37 nmol h/l;P= 0·02).Conclusions40‐20‐0 mg immediate release, but not modified release hydrocortisone, resulted in sufficient glucocorticoid coverage in patients with ACC receiving mitotane treatment. The use of equivalent doses of modified release hydrocortisone preparation should be avoided in patients on mitotane treatment.