Absorption, Distribution and Excretion
Intramuscular injection of corticotropin results in rapid absorption; sustained-release formulations are absorbed slowly over approximately 8 to 16 hours. In the bloodstream, corticotropin is transported along with Cohn protein components II and III. The exact distribution and metabolic pathways of this drug are not fully understood, but it is rapidly cleared from plasma by many tissues. Corticotropin appears not to cross the placenta. Circulating corticotropin may be enzymatically cleaved by the plasmin-plasminogen system at the 16-17 lysine-arginine bond. In patients with normal adrenal cortex function, plasma cortisol concentrations typically peak within 1 hour after intramuscular or rapid direct intravenous injection of 25 units of corticotropin and begin to decline after 2-4 hours. A study in healthy subjects showed that subcutaneous injection of 80 units of corticotropin resulted in peak plasma 17-hydroxycorticosteroid (17-OHCS) concentrations within 3-12 hours and returned to baseline levels within 10-25 hours. Oral corticotropin is inactivated by proteolytic enzymes in the gastrointestinal tract, therefore topical application to the skin or eyes is ineffective. Following intramuscular injection of corticotropin (ACTH), the drug is rapidly absorbed. The absorption time after an intramuscular injection of ACTH is approximately 8-16 hours. For most adults with normal adrenal function, maximal adrenal stimulation is achieved 8 hours after an intravenous infusion of 1-6 units of ACTH (currently discontinued in the US). At a fixed dose, ACTH injection, when administered slowly intravenously or as a drug reserve rather than directly, more effectively stimulates cortisol secretion compared to rapid intravenous injection. Increasing the intramuscular or intravenous dose prolongs the duration of action. Repeated intravenous injections of ACTH over 8 hours for several consecutive days enhance the adrenal cortex's responsiveness to further drug stimulation. In patients with normal adrenal function, an intramuscular injection of 100 units of ACTH (as a drug reserve) results in approximately 100 mg of cortisol secretion within 16 hours. In patients with normal adrenal function, plasma cortisol concentrations peak within 1 hour after an intramuscular or rapid direct intravenous injection of 25 units of ACTH and begin to decline after 2 hours. A study in healthy subjects showed that after subcutaneous injection of 80 units of adrenocorticotropic hormone (ACTH), plasma 17-hydroxycorticosteroid (17-OHCS) concentrations peaked within 3–12 hours and returned to baseline levels within 10–25 hours. ACTH is rapidly cleared from the bloodstream after intravenous injection…

---

Biological Half-Life
Approximately 15 minutes after intravenous injection... In the human body, the plasma half-life is approximately 15 minutes.

Effects During Pregnancy and Lactation
◉ Overview of Medication Use During Lactation
Currently, there is no information regarding the clinical use of corticotropin (ACT) during lactation. Due to its large molecular weight (4541 Da), ACTP is unlikely to be present in breast milk. The likelihood of infants absorbing ACTP is also low, as it is likely to be destroyed in the infant's gastrointestinal tract, and oral absorption is very low. Furthermore, ACTP has a half-life of only 10 to 15 minutes. Animal studies have shown that cortisol levels in breast milk may increase after a lactating mother takes ACTP.
◉ Effects on Breastfed Infants
As of the revision date, no relevant published information was found.
◉ Effects on Lactation and Breast Milk
As of the revision date, no relevant published information was found.

---

Interactions
Concomitant use of ulcer-inducing drugs such as salicylates or indomethacin with corticotropin may increase the risk of gastrointestinal ulcers. Furthermore, caution should be exercised when using aspirin and corticotropin together in patients with hypoprothrombinemia. Glucocorticoids may also lower blood salicylate levels. Discontinuing corticotropin in patients taking both medications concurrently and with stable conditions may lead to salicylate toxicity. Estrogens may enhance the effects of cortisol, possibly by increasing the concentration of cortisol transporters, thereby reducing the amount of cortisol available for metabolism. Adding or discontinuing estrogen in a stable corticotropin regimen may require adjustments to the corticotropin dosage. Barbiturates, phenytoin sodium, and rifampin, which can induce liver enzymes, may increase glucocorticoid metabolism; therefore, adding or discontinuing such drugs in a stable corticotropin regimen may reduce the efficacy of corticosteroids. Corticosteroids may inhibit liver enzymes that activate cyclophosphamide to alkylating metabolites; therefore, changes in cyclophosphamide efficacy should be monitored if corticotropin is used concurrently. In rare cases, corticotropin has been reported to increase blood coagulability and oral anticoagulant dosage requirements in some patients; bleeding has occurred in other patients receiving both oral anticoagulants and corticotropin. Because the clinical significance of these interactions is not yet established, caution should be exercised when initiating or discontinuing corticotropin therapy in stable patients receiving oral anticoagulants. Potassium-depleting diuretics (such as thiazide diuretics, furosemide, and ethacrynic acid) and other potassium-depleting agents, such as amphotericin B, can enhance the potassium-depleting effect of corticotropin. Furthermore, amphotericin B may reduce the responsiveness of the adrenal cortex to corticotropin. Serum potassium levels should be closely monitored in patients receiving both corticotropin and potassium-depleting agents.

[1]. Syndrome de résistance à l’Adrénocorticotrophine Hormone (ACTH): à propos d’un cas [Adrenocorticotropic hormone (ACTH) insensitivity syndrome: about a case]. Pan Afr Med J. 2018 Aug 2;30:244. French.

[2]. The effect of adrenocorticotrophic hormone on the yield, composition and butterfat properties of cow's milk. Journal of Dairy Research. 1964, 31(1), 71-79.

Corticotropin (ACTH) is a polypeptide hormone produced and secreted by the pituitary gland, composed of 39 linearly arranged amino acid residues. Its N-terminal 24-amino acid segment is identical in all species and possesses adrenocorticotropic hormone (ACTH) activity. ACTH stimulates the adrenal cortex, promoting the synthesis of corticosteroids (primarily glucocorticoids, but also including sex hormones (androgens)). It is used to treat certain neurological disorders, such as infantile spasms and multiple sclerosis, and also to diagnose adrenal insufficiency. It is a diagnostic reagent. It is a polypeptide, peptide hormone, and biological macromolecule. ACTH is an anterior pituitary hormone that stimulates the adrenal cortex and its production of corticosteroids. ACTH is a polypeptide composed of 39 amino acids, with its N-terminal 24-amino acid segment identical in all species and possessing adrenocorticotropic hormone activity. After further tissue-specific processing, ACTH can generate α-MSH and adrenocorticotropic hormone-like intermediate lobe peptide (CLIP). See also: Corticotropin (note moved to); Corticotropin library (note moved to).

C207H308N56O58S

4541.06586551666

4538.26

9002-60-2

Adrenocorticotropic hormone TFA

16132265

White to off-white solid powder

5.654

63

68

148

322

11200

36

S(C)CC[C@@H](C(N[C@@H](CCC(=O)O)C(N[C@@H](CC1=CN=CN1)C(N[C@@H](CC1C=CC=CC=1)C(N[C@@H](CCCNC(=N)N)C(N[C@@H](CC1=CNC2C=CC=CC1=2)C(NCC(N[C@@H](CCCCN)C(N1CCC[C@H]1C(N[C@H](C(NCC(N[C@@H](CCCCN)C(N[C@@H](CCCCN)C(N[C@@H](CCCNC(=N)N)C(N[C@@H](CCCNC(=N)N)C(N1CCC[C@H]1C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@@H](CC1C=CC(=CC=1)O)C(N1CCC[C@H]1C(N[C@H](C(NCC(N[C@H](C(N[C@H](C(N[C@@H](CC(=O)O)C(N[C@@H](CCC(=O)O)C(N[C@@H](CO)C(N[C@@H](C)C(N[C@@H](CCC(=O)O)C(N[C@@H](C)C(N[C@@H](CC1C=CC=CC=1)C(N1CCC[C@H]1C(N[C@H](C(N[C@H](C(N[C@H](C(=O)O)CC1C=CC=CC=1)=O)CCC(=O)O)=O)CC(C)C)=O)=O)=O)=O)=O)=O)=O)=O)=O)CCC(=O)O)=O)C)=O)=O)CC(N)=O)=O)=O)=O)C(C)C)=O)CCCCN)=O)C(C)C)=O)=O)=O)=O)=O)=O)=O)C(C)C)=O)=O)=O)=O)=O)=O)=O)=O)=O)NC([C@H](CO)NC([C@H](CC1C=CC(=CC=1)O)NC([C@H](CO)N)=O)=O)=O

IDLFZVILOHSSID-OVLDLUHVSA-N

InChI=1S/C207H308N56O58S/c1-108(2)89-140(186(302)240-135(69-74-163(279)280)182(298)254-149(204(320)321)94-117-43-20-15-21-44-117)250-193(309)152-54-35-86-262(152)202(318)147(92-116-41-18-14-19-42-116)252-171(287)114(11)230-175(291)132(66-71-160(273)274)234-170(286)113(10)231-191(307)150(105-265)255-183(299)136(70-75-164(281)282)241-190(306)146(98-165(283)284)249-180(296)133(67-72-161(275)276)235-169(285)112(9)229-157(270)101-225-174(290)145(97-156(213)269)251-194(310)153-55-36-87-263(153)203(319)148(93-119-60-64-123(268)65-61-119)253-199(315)167(110(5)6)257-185(301)129(49-26-30-79-210)243-198(314)168(111(7)8)259-196(312)155-57-38-85-261(155)201(317)139(53-34-83-223-207(218)219)244-178(294)130(51-32-81-221-205(214)215)237-177(293)128(48-25-29-78-209)236-176(292)127(47-24-28-77-208)232-158(271)103-227-197(313)166(109(3)4)258-195(311)154-56-37-84-260(154)200(316)138(50-27-31-80-211)233-159(272)102-226-173(289)143(95-120-99-224-126-46-23-22-45-124(120)126)247-179(295)131(52-33-82-222-206(216)217)238-187(303)142(90-115-39-16-13-17-40-115)246-189(305)144(96-121-100-220-107-228-121)248-181(297)134(68-73-162(277)278)239-184(300)137(76-88-322-12)242-192(308)151(106-266)256-188(304)141(245-172(288)125(212)104-264)91-118-58-62-122(267)63-59-118/h13-23,39-46,58-65,99-100,107-114,125,127-155,166-168,224,264-268H,24-38,47-57,66-98,101-106,208-212H2,1-12H3,(H2,213,269)(H,220,228)(H,225,290)(H,226,289)(H,227,313)(H,229,270)(H,230,291)(H,231,307)(H,232,271)(H,233,272)(H,234,286)(H,235,285)(H,236,292)(H,237,293)(H,238,303)(H,239,300)(H,240,302)(H,241,306)(H,242,308)(H,243,314)(H,244,294)(H,245,288)(H,246,305)(H,247,295)(H,248,297)(H,249,296)(H,250,309)(H,251,310)(H,252,287)(H,253,315)(H,254,298)(H,255,299)(H,256,304)(H,257,301)(H,258,311)(H,259,312)(H,273,274)(H,275,276)(H,277,278)(H,279,280)(H,281,282)(H,283,284)(H,320,321)(H4,214,215,221)(H4,216,217,222)(H4,218,219,223)/t112-,113-,114-,125-,127-,128-,129-,130-,131-,132-,133-,134-,135-,136-,137-,138-,139-,140-,141-,142-,143-,144-,145-,146-,147-,148-,149-,150-,151-,152-,153-,154-,155-,166-,167-,168-/m0/s1

(4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-4-amino-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[2-[[(2S)-2-[[(2S)-1-[(2S)-6-amino-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-4-carboxybutanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]acetyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]acetyl]amino]hexanoyl]amino]hexanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]hexanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carbonyl]amino]-4-oxobutanoyl]amino]acetyl]amino]propanoyl]amino]-4-carboxybutanoyl]amino]-3-carboxypropanoyl]amino]-4-carboxybutanoyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-[[(2S)-1-[[(2S)-1-[(2S)-2-[[(2S)-1-[[(2S)-4-carboxy-1-[[(1S)-1-carboxy-2-phenylethyl]amino]-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopropan-2-yl]amino]-5-oxopentanoic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

---

Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

View More

Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

---

Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

View More

Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

---

Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

---

 (Please use freshly prepared in vivo formulations for optimal results.)