Burger-Stritt Stephanie, Bachmann Linda, Kurlbaum Max, Hahner Stefanie
Endocrinology and Diabetes Unit, Department of Medicine I, University Hospital Wuerzburg, Wuerzburg, Germany.
Endocr Connect. 2019 Apr 1;8(4):425-434. doi: 10.1530/EC-19-0024.
Objective Patients with adrenal insufficiency (AI) need to adapt their glucocorticoid replacement under stressful conditions to prevent adrenal crisis (AC). Prednisone (PN) suppositories are used for emergency treatment. Pharmacokinetics of 100 mg PN suppositories after vaginal or rectal administration was evaluated. Design Single-center, open-label, sequence-randomized, cross-over, bioequivalence study. Methods Twelve females with primary AI were included. Comparison of pharmacokinetics after vaginal and rectal administration of 100 mg PN suppositories. Main outcome measures: bioequivalence (Cmax: maximum plasma concentration of prednisolone; AUC0 -360: area under the plasma concentration curve of prednisolone from administration to 360 min), adrenocorticotropin (ACTH) levels, safety and tolerability. Comparison of ACTH-suppressive effect with subcutaneous and intramuscular administration of 100 mg hydrocortisone. Results Vaginal administration of PN suppositories was not bioequivalent to rectal administration: Cmax and AUC0-360 were significantly lower after vaginal compared to rectal administration: 22 ng/mL (109%) vs 161 ng/mL (28%), P < 0.001; 4390 ng/mL * min (116%) vs 40,302 ng/mL * min (26%), P < 0.001; (mean (coefficient of variation), respectively). A suppression of ACTH by >50% of baseline values was observed 149 min (32%) after rectal PN administration; after vaginal PN administration, the maximum decrease within 360 min was only 44%. Adverse events were more frequent after vaginal administration and mainly attributable to the glucocorticoid deficit due to inadequate vaginal absorption. The ACTH-suppressive effect was more pronounced after parenteral hydrocortisone compared to rectal or vaginal PN. Conclusion Vaginal administration of PN suppositories in the available form is not useful for prevention of AC. Pharmacokinetics after rectal use of PN show inferiority compared to available data on parenteral glucocorticoids. In adrenal emergencies, hydrocortisone injection should be the first choice.
肾上腺功能不全（AI）患者在应激状态下需要调整糖皮质激素替代治疗以预防肾上腺危象（AC）。泼尼松（PN）栓剂用于紧急治疗。评估了100mg PN栓剂经阴道或直肠给药后的药代动力学。
单中心、开放标签、序列随机、交叉、生物等效性研究。
纳入12名原发性AI女性患者。比较100mg PN栓剂经阴道和直肠给药后的药代动力学。主要观察指标：生物等效性（Cmax：泼尼松龙的最大血浆浓度；AUC0 - 360：从给药至360分钟泼尼松龙血浆浓度曲线下面积）、促肾上腺皮质激素（ACTH）水平、安全性和耐受性。比较经直肠和阴道给药100mg PN栓剂与皮下和肌肉注射100mg氢化可的松的ACTH抑制作用。
PN栓剂经阴道给药与经直肠给药不具有生物等效性：与经直肠给药相比，经阴道给药后的Cmax和AUC0 - 360显著更低：分别为22ng/mL（109%）对161ng/mL（28%），P < 0.001；4390ng/mL·min（116%）对40302ng/mL·min（26%），P < 0.001；（分别为平均值（变异系数））。经直肠给予PN后149分钟（32%）观察到ACTH抑制超过基线值的50%；经阴道给予PN后，360分钟内的最大降幅仅为44%。经阴道给药后不良事件更频繁，主要归因于阴道吸收不足导致的糖皮质激素缺乏。与经直肠或阴道给予PN相比，胃肠外给予氢化可的松后的ACTH抑制作用更明显。
现有剂型的PN栓剂经阴道给药对预防AC无效。与胃肠外糖皮质激素的现有数据相比，经直肠使用PN后的药代动力学表现较差。在肾上腺急症中，氢化可的松注射应作为首选。
