Development Planning, Clinical Development Center, Asahi Kasei Pharma Corporation, Chiyoda-ku, Tokyo, Japan.
Pharmaspur Inc., Tokyo, Japan.
Clin Pharmacol Drug Dev. 2022 Sep;11(9):1092-1098. doi: 10.1002/cpdd.1101. Epub 2022 Apr 11.
Isavuconazonium sulfate is the water-soluble prodrug of the novel, broad-spectrum, triazole antifungal agent isavuconazole. A size 0 elongated hard capsule containing 100 mg equivalent of isavuconazole is the currently marketed oral formulation in countries where it is approved. An alternative oral formulation, based on a lower-strength and smaller-size capsule, is required for pediatric and adolescent patients, as well as for some adult Japanese patients, especially those with difficulties swallowing larger capsules. This study was conducted to evaluate the bioequivalence of a size 0 elongated capsule containing 100 mg equivalent of isavuconazole and a size 3 capsule containing 40 mg equivalent of isavuconazole, after administration of 200 mg equivalent of isavuconazole (5 size 3 capsules or 2 size 0 elongated capsules) under fasted conditions. Bioequivalence of isavuconazole between the formulations was demonstrated, since point estimates (90%CI) for the ratio of the size 0 elongated capsules vs the size 3 capsules for maximum plasma concentration and area under the plasma concentration-time curve from time 0 to the last quantifiable concentration were within the acceptable range of 0.8 to 1.25. It was confirmed that both formulations were well tolerated, and no new safety signals were observed in healthy Japanese adult male subjects.
硫酸伊曲康唑是新型广谱三唑类抗真菌药物伊曲康唑的水溶性前体药物。在已批准上市的国家，含有 100 毫克等效伊曲康唑的 0 号长椭圆形硬胶囊是目前上市的口服制剂。儿科和青少年患者以及一些成年日本患者（尤其是吞咽较大胶囊有困难的患者）需要一种基于低强度和较小胶囊的替代口服制剂。这项研究旨在评估在空腹条件下给予 200 毫克等效伊曲康唑（5 个 3 号胶囊或 2 个 0 号长椭圆形胶囊）后，含有 100 毫克等效伊曲康唑的 0 号长椭圆形胶囊和含有 40 毫克等效伊曲康唑的 3 号胶囊的生物等效性。两种制剂的伊曲康唑的生物等效性得到了证明，因为最大血浆浓度和从 0 时间到最后可定量浓度的血浆浓度-时间曲线下面积的 0 号长椭圆形胶囊与 3 号胶囊比值的点估计值（90%置信区间）在 0.8 到 1.25 的可接受范围内。结果证实两种制剂均具有良好的耐受性，在健康日本成年男性受试者中未观察到新的安全性信号。
