Comparative trial with highly purified natural ACTH, synthetic ACTH 1—24 peptide and synthetic ACTH 1—39 peptide

Abstract

Brombacher, Buytendijk and Maesen: Comparative trial with natural ACTH and synthetic ACTH peptides 291 Z. klin. Chem. u. klin. Biochem. 7. Jg., S. 291-292, Mai 1969 Comparative trial with highly purified natural ACTH, synthetic ACTH 1-24 peptide and synthetic ACTH 1-39 peptide The intensity and duration of the adrenocortical stimulation^ produced by highly purified natural porcine ACTH (44 U/m/), synthetic ACTH 1-24 peptide (0.44 mg tetracosapeptide/m/) and synthetic ACTH 1-39 peptide (0.4 mg l-39 peptide/m/) with all preparations dissolved in a gelatin solution, \vere investigated in one trial with a total of 18 healthy volunteers. The activity of synthetic ACTH 1-39 peptide significantly exceeds that of the synthetic 1-24 peptide, but is of shorter duration than that of the natural peptide. During long term treatment of patients with corticosteroids many clinicians require a means of reactivating the adrenal cortex which is therapeutically more or less suppressed. This is notably the case in the treatment of bronchial asthma, rheumatic disease and simular affections. Up till some years ago some more or less highly purified corticotropin preparations of animal origin were frequently used for the stimulation of the adrenal cortex. As a matter of fact there was always the danger of sensitising the patient towards the animal protein with all the unwanted consequences such as anaphylactic shock in all its forms. These effects were seen indeed in about five percent of people repeatedly undergoing this therapy (1, 2). For those reasons an iatrogenically inactivated adrenal cortex was often preferred as presenting a less serious risk than that accompanying regular administration of non-human protein hormone. This deadlock was solved by the availability of a polypeptide with corticotropic activity synthesized by SCHWYZER and KAPPELER (3). This peptide of fully synthetic origin did not induce sensibilization which · was also demonstrated with skin tests on patients known to react allergically to animal corticotropin (4). The non appearance of reactions came up to expectations because the sequence of the 24 amino acids of the synthetic product is the same as that in part of the natural ACTH molecule for many animal species and man (5). A certain disappointment however was felt when it became evident that the duration of action of the synthetic peptide was much shorter than for the natural hormone. Nevertheless with adequate dosage the effect was the same for both preparations for some hours after intravenous or intramuscular administration as measured by the increase of plasma cortisol levels. As was expected a very satisfactory effect was seen on continuous intravenous infusion (6), but there are practical objections to this. Consequently a definite want is felt for a synthetic preparation comparable to natural corticotropin with respect to duration of action and adrenal cortex stimulatory effect, but without the allergic properties of the latter. Possibly the shorter duration of action of the synthetic 24 amino aci...

Pharmacokinetics and Pharmacodynamics of Repository Corticotropin Injection Compared With Synthetic ACTH1‐24 Depot and Methylprednisolone in Healthy Subjects

“…Since therapeutic use of ACTH analog formulations became widespread in the 1950s and 1960s, studies have demonstrated variable cortisol responses after administration of different ACTH products. 24 , 25 , 33 , 34 This phase 1, single‐center, open‐label, randomized parallel group study is the first to report a direct comparison of the cortisol responses of RCI and synthetic ACTH 1‐24 depot.…”

Comparison of Steroidogenic Exposure Following the Administration of Repository Corticotropin Injection With a Synthetic ACTH1‐24 Depot and Methylprednisolone in Healthy Subjects

“…Endogenous ACTH potently induces cortisol production 25 ; however, the steroidogenic effects of different ACTH drug class formulations are known to be variable. 20 , 26 For example, a comparison of synthetic ACTH 1‐24 , synthetic ACTH 1‐39 , and a porcine‐derived ACTH formulation (Organon, Inc.) demonstrated a higher corticosteroid response with the porcine‐derived ACTH than with the other ACTH formulations. 26 These data are in contrast to our results showing that synthetic ACTH 1‐24 depot was more steroidogenic than repository corticotropin injection.…”

“… 20 , 26 For example, a comparison of synthetic ACTH 1‐24 , synthetic ACTH 1‐39 , and a porcine‐derived ACTH formulation (Organon, Inc.) demonstrated a higher corticosteroid response with the porcine‐derived ACTH than with the other ACTH formulations. 26 These data are in contrast to our results showing that synthetic ACTH 1‐24 depot was more steroidogenic than repository corticotropin injection. In addition, the corticosteroid response to the synthetic ACTH 1‐24 depot used in our study and the ACTH 1‐24 used by Brombacher et al were similar, suggesting that the porcine‐derived ACTH formulation studied by Brombacher induces a greater corticosteroid response than repository corticotropin injection.…”

A Systematic Literature Review and Indirect Treatment Comparison of Efficacy of Repository Corticotropin Injection versus Synthetic Adrenocorticotropic Hormone for Infantile Spasms

“…12 ACTH is available as a natural product and as a synthetic analog. 13 Outside the United States, synthetic analogs of ACTH-synthetic ACTH 1-24 (tetracosactide) and synthetic ACTH 1-39 (corticotropin carboxymethyl-cellulose [CCMC])-are used. 6,14 The efficacy of RCI may differ from that of synthetic ACTH treatments based on the structure of peptide; 15 however, there are no head-to-head trials comparing the efficacy of RCI and synthetic ACTH treatments.…”