期刊
CLINICAL PHARMACOLOGY IN DRUG DEVELOPMENT
卷 11, 期 4, 页码 502-515出版社
WILEY
DOI: 10.1002/cpdd.1020
关键词
pharmacodynamics; pharmacokinetics; RCI; repository corticotropin injection; synthetic ACTH(1-24) depot
资金
- Mallinckrodt Pharmaceuticals
The study compared the pharmacokinetics and pharmacodynamics of Repository corticotropin injection (RCI) and synthetic ACTH(1-24) depot, finding that RCI led to significantly lower free cortisol exposure and steroidogenic exposure compared to synthetic ACTH(1-24) depot, suggesting that they are not interchangeable in their pharmacological properties.
Repository corticotropin injection (RCI; Acthar Gel) is a naturally sourced complex mixture of adrenocorticotropic hormone (ACTH) analogs and other pituitary peptides. This phase 1, single-center, open-label, randomized parallel study directly compared the pharmacokinetics and pharmacodynamics of RCI and synthetic ACTH(1-24) depot. Methylprednisolone was included to estimate the steroidogenic exposure of RCI and synthetic ACTH(1-24) depot when used to treat nephrotic syndrome. A total of 48 healthy subjects aged 18 to 50 years were randomly assigned 1:1:1 to RCI (80 IU subcutaneously twice weekly on study days 1 and 4), synthetic ACTH(1-24) depot (1 mg subcutaneously twice weekly on study days 1 and 4), or methylprednisolone (32 mg orally once daily on study days 1 through 6). After 2 doses, RCI induced about 5-fold lower free cortisol exposure and an estimated 4-fold lower steroidogenic exposure than synthetic ACTH(1-24) depot. The lower endogenous cortisol response of RCI was achieved despite higher observed mean plasma concentrations of N25-deamidated porcine ACTH(1-39) (the pharmacokinetic marker for RCI) than of ACTH(1-24). The different pharmacodynamic properties demonstrated by RCI and synthetic ACTH(1-24) depot in this study suggest that these products in the ACTH class are not interchangeable.
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