title: Pharmacodynamics and tolerability of repository corticotropin injection in healthy human subjects: A comparison with intravenous methylprednisolone.
abstract: Repository corticotropin injection (porcine adrenocorticotropic hormone [ACTH] analog) and intravenous methylprednisolone (IVMP) are used to treat inflammatory conditions such as multiple sclerosis (MS) exacerbations and rheumatoid arthritis. This multiple-dose, randomized, crossover, open-label study evaluated and compared pharmacodynamic outcomes in subjects who received ACTH analog (80 U subcutaneously) or IVMP (1 g) daily for 5 days. Specific outcome measures included IVMP and cortisol concentrations, total cortisol-equivalent exposure, immune cell population changes, and tolerability. IVMP and ACTH analog increased granulocyte numbers and decreased lymphocyte counts; effects on both were significantly less pronounced with ACTH analog. Based on total cortisol-equivalent exposure (assuming linearity), administration of 80 U of ACTH analog equates to 30 mg IVMP. Because IVMP doses significantly higher than 30 mg are usually required to treat MS exacerbations, the lower cortisol-equivalent exposure of 80 U ACTH analog supports the hypothesis that efficacy of ACTH analog results from both steroid-dependent and -independent properties. Adverse events were mild in severity; subject incidence for adverse-event reporting was similar following both regimens. The clinical relevance of these findings in autoimmune disease populations is unknown and requires further evaluation.
authors.affiliation: Mallinckrodt Pharmaceuticals, Ellicott City, MD, USA.
authors.forename: Ritu
authors.initials: R
authors.lastname: Lal
authors.affiliation: Mallinckrodt Pharmaceuticals, Ellicott City, MD, USA.
authors.forename: Stacie
authors.initials: S
authors.lastname: Bell
authors.affiliation: Mallinckrodt Pharmaceuticals, Ellicott City, MD, USA.
authors.forename: Rashida
authors.initials: R
authors.lastname: Challenger
authors.affiliation: Mallinckrodt Pharmaceuticals, Ellicott City, MD, USA.
authors.forename: Vakessa
authors.initials: V
authors.lastname: Hammock
authors.affiliation: Mallinckrodt Pharmaceuticals, Ellicott City, MD, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Nyberg
authors.affiliation: Mallinckrodt Pharmaceuticals, Ellicott City, MD, USA.
authors.forename: Dima
authors.initials: D
authors.lastname: Decker
authors.affiliation: Mallinckrodt Pharmaceuticals, Ellicott City, MD, USA.
authors.forename: Patrice M
authors.initials: PM
authors.lastname: Becker
authors.affiliation: Mallinckrodt Pharmaceuticals, Ellicott City, MD, USA.
authors.forename: David
authors.initials: D
authors.lastname: Young
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000009:adverse effects* / Q000494:pharmacology*; D000328:Adult; D018592:Cross-Over Studies; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007275:Injections, Intravenous; D007958:Leukocyte Count; D007962:Leukocytes / Q000187:drug effects; D008775:Methylprednisolone / Q000009:adverse effects* / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone; D008775:Methylprednisolone
keywords: biomarkers; clinical pharmacology; clinical research; pharmacodynamics; pharmacology