Babadjanova G, Allolio B, Vollmer M, Reincke M, Schulte H M
Medizinische Universitätsklinik Würzburg, Germany.
Eur J Clin Pharmacol. 1996;51(1):53-7. doi: 10.1007/s002280050160.
Deflazacort, a synthetic oxazoline derivative of prednisolone, has been suggested as having major advantages over other glucocorticoids, as it is claimed to cause fewer adverse effects at equivalent antiinflammatory potency. The assumed equipotency ratio of deflazacort versus other glucocorticoids is critical for this assumption.
In a randomized cross-over study we compared the acute effects of deflazacort and prednisolone on serum cortisol, osteocalcin, insulin and blood cells (eosinophils and lymphocytes) in normal subjects. On seven occasions separated by a wash out period > or = 1 week all participants received placebo, prednisolone (8 mg, 20 mg, 40 mg) and deflazacort (12 mg, 30 mg, 60 mg). The medication was given orally at 20.00 h as a single dose. Blood was collected at 8.00 h before and after each medication. Log (dose) response relationships were calculated and were used to compare the drugs.
The following equipotent dose ratios (mg deflazacort: mg prednisolone) were found: osteocalcin suppression 1.54, cortisol suppression 2.27, suppression of eosinophils 1.14 and lymphocytes 2.77. As parallelism between regression curves was rejected, equipotency could not be calculated for insulin. In 3 subjects even the highest dose of deflazacort failed to suppress serum cortisol.
Our study highlights the difficulties of establishing equipotency ratios for glucocorticoids. It casts doubts on the generally assumed equipotency dose ratio of deflazacort vs prednisolone, as both for cortisol and lymphocytes the 95% CI was > 1.2. Thus, reduced adverse effects during deflazacort therapy may be a consequence of lower effective glucocorticoid dosage.
地夫可特是泼尼松龙的一种合成恶唑啉衍生物，据称与其他糖皮质激素相比具有主要优势，因为在同等抗炎效力下它被认为产生的不良反应更少。地夫可特与其他糖皮质激素的假定等效剂量比对于这一假设至关重要。
在一项随机交叉研究中，我们比较了地夫可特和泼尼松龙对正常受试者血清皮质醇、骨钙素、胰岛素和血细胞（嗜酸性粒细胞和淋巴细胞）的急性影响。在7个时间点，间隔洗脱期≥1周，所有参与者接受安慰剂、泼尼松龙（8毫克、20毫克、40毫克）和地夫可特（12毫克、30毫克、60毫克）。药物于20:00口服，为单剂量。在每次用药前后的8:00采集血液。计算对数（剂量）反应关系并用于比较药物。
发现以下等效剂量比（地夫可特毫克数：泼尼松龙毫克数）：骨钙素抑制为1.54，皮质醇抑制为2.27，嗜酸性粒细胞抑制为1.14，淋巴细胞抑制为2.77。由于回归曲线之间缺乏平行性，无法计算胰岛素的等效剂量。在3名受试者中，即使是最高剂量的地夫可特也未能抑制血清皮质醇。
我们的研究凸显了确定糖皮质激素等效剂量比的困难。它对地夫可特与泼尼松龙通常假定的等效剂量比提出了质疑，因为对于皮质醇和淋巴细胞，95%置信区间均>1.2。因此，地夫可特治疗期间不良反应减少可能是糖皮质激素有效剂量较低的结果。
