Insulin human

DB00030

biotech approved investigational

Deskripsi

Human Insulin, also known as Regular Insulin, is a short-acting form of insulin used for the treatment of hyperglycemia caused by Type 1 and Type 2 Diabetes. Human insulin is produced by recombinant DNA technology and is identical to endogenously produced insulin. Typically prescribed for the management of diabetes mellitus, insulin is a peptide hormone produced by beta cells of the pancreas that promotes glucose metabolism. Insulin is released from the pancreas following a meal to promote the uptake of glucose from the blood into internal organs and tissues such as the liver, fat cells, and skeletal muscle. Absorption of glucose into cells allows for its transformation into glycogen or fat for storage. Insulin also inhibits hepatic glucose production, enhances protein synthesis, and inhibits lipolysis and proteolysis among many other functions.

Insulin is an important treatment in the management of Type 1 Diabetes (T1D) which is caused by an autoimmune reaction that destroys the beta cells of the pancreas, resulting in the body not being able to produce or synthesize the insulin needed to manage circulating blood sugar levels. As a result, people with T1D rely primarily on exogenous forms of insulin to lower glucose levels in the blood. Insulin is also used in the treatment of Type 2 Diabetes (T2D), another form of diabetes mellitus that is a slowly progressing metabolic disorder caused by a combination of genetic and lifestyle factors that promote chronically elevated blood sugar levels. Without treatment or improvement in non-pharmacological measures such as diet and exercise to lower blood glucose, high blood sugar eventually causes cellular resistance to endogenous insulin, and in the long term, damage to pancreatic islet cells. Insulin is typically prescribed later in the course of T2D, after trying several oral medications such as DB00331, DB01120, or DB01261 have been tried, when sufficient damage has been caused to pancreatic cells that the body is no longer able to produce insulin on its own.

Marketed as the brand name product Humulin R or Novolin R, human insulin begins to exert its effects within 30 minutes of subcutaneous administration, while peak levels occur 3-4 hours after administration. Due to its quick onset of action, human insulin is considered "bolus insulin" as it provides high levels of insulin in a short period of time to mimic the release of endogenous insulin from the pancreas after meals. Bolus insulin is often combined with once daily, long-acting "basal insulin" such as DB01307, DB09564, and DB00047 to provide low concentrations of background insulin that can keep blood sugar stable between meals or overnight. Use of basal and bolus insulin together is intended to mimic the pancreas' production of endogenous insulin, with a goal of avoiding any periods of hypoglycemia.

Human insulin is also available in an inhalable form, intended to be used as a bolus meal-time insulin. Exubera was the first inhaled insulin available on the market and was developed by Inhale Therapeutics (later named Nektar Therapeutics). Unfortunately, limited uptake by physicians and patients, poor sales, bulky packaging, and concerns over the possible impact on lung cancer development resulted in Exubera products being withdrawn from the US markets A176005. Exubera was followed by Afrezza, a monomeric inhaled insulin developed by Mannkind Corporation, which received FDA approval in 2016. While still available in the US, Afrezza has had similar concerns associated with its use, and had an FDA "black box" warning added to it to warn about use in patients with chronic lung disease. Afrezza does not currently have Health Canada or European Medicines Agency approval for marketing in Canada or the EU.

Human Insulin is a 51 residue peptide hormone produced by recombinant DNA technology by inserting the human insulin gene into Escherichia coli bacteria or Saccharomyces cerevisiae. The structure is identical to native human insulin, with two amino acid chains covalently linked by disulfide bonds.

Human insulin is also available in an intermediate-acting form as NPH (Neutral Protamine Hagedorn) as the marketed products Novolin N and Humulin N. NPH insulin is provided as a crystalline suspension of insulin with protamine and zinc, resulting in an onset of action in 1 to 3 hours, duration of action up to 24 hours, and peak action from 6 to 8 hours. Due to the added crystals, NPH insulin is typically cloudy when compared to other forms of insulin and has a neutral pH.

Without an adequate supply of insulin to promote absorption of glucose from the bloodstream, blood sugar levels can climb to dangerously high levels and can result in symptoms such as fatigue, headache, blurred vision, and increased thirst. If left untreated, the body starts to break down fat, instead of glucose, for energy which results in a build-up of ketone acids in the blood and a syndrome called ketoacidosis, which is a life-threatening medical emergency. In the long term, elevated blood sugar levels increase the risk of heart attack, stroke, and diabetic neuropathy.

Struktur Molekul 2D

Struktur tidak tersedia

Peta Jejaring Molekuler
Legenda: ObatTargetGenEnzim(Panah → menunjukkan arah efek / relasi)TransporterCarrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) Systemic insulin disposition (apparent terminal half-life) following oral inhalation of 4 to 48 units of human insulin was 120-206 minutes.
Volume Distribusi -
Klirens (Clearance) -

Absorpsi

When injected subcutaneously, the glucose-lowering effect of human insulin begins approximately 30 minutes post-dose. After a single subcutaneous administration of 0.1 unit/kg of human insulin to healthy subjects, peak insulin concentrations occurred between 1.5 to 2.5 hours post-dose. When administered in an inhaled form (as the product Afrezza), the time to maximum serum insulin concentration ranges from 10-20 minutes after oral inhalation of 4 to 48 units of human insulin. Serum insulin concentrations declined to baseline by approximately 60-240 minutes for these dose levels. Intrapatient variability in insulin exposure measured by AUC and Cmax is approximately 16% (95% CI 12-23%) and 21% (95% CI 16-30%), respectively.

Metabolisme

The metabolism and elimination of orally inhaled human insulin are comparable to regular human insulin.

Rute Eliminasi

Following oral inhalation of human insulin, a mean of 39% of the inhaled dose of carrier particles was distributed to the lungs and a mean of 7% of the dose was swallowed. The swallowed fraction was not absorbed from the GI tract and was eliminated unchanged in the feces.

Interaksi Makanan

1 Data
  • 1. Avoid alcohol. Alcohol may impair blood glucose control.

Interaksi Obat

791 Data
Liraglutide Liraglutide may increase the hypoglycemic activities of Insulin human.
Metreleptin Metreleptin may increase the hypoglycemic activities of Insulin human.
Pegvisomant The risk or severity of hypoglycemia can be increased when Pegvisomant is combined with Insulin human.
Pioglitazone The risk or severity of adverse effects can be increased when Pioglitazone is combined with Insulin human.
Pramlintide Pramlintide may increase the hypoglycemic activities of Insulin human.
Rosiglitazone The risk or severity of congestive heart failure can be increased when Insulin human is combined with Rosiglitazone.
Lipoic acid The risk or severity of hypoglycemia can be increased when Lipoic acid is combined with Insulin human.
Edetic acid Edetic acid may increase the hypoglycemic activities of Insulin human.
Esmolol Esmolol may increase the hypoglycemic activities of Insulin human.
Landiolol Landiolol may increase the hypoglycemic activities of Insulin human.
Moxifloxacin The therapeutic efficacy of Insulin human can be increased when used in combination with Moxifloxacin.
Grepafloxacin The therapeutic efficacy of Insulin human can be increased when used in combination with Grepafloxacin.
Enoxacin The therapeutic efficacy of Insulin human can be increased when used in combination with Enoxacin.
Pefloxacin The therapeutic efficacy of Insulin human can be increased when used in combination with Pefloxacin.
Ciprofloxacin The therapeutic efficacy of Insulin human can be increased when used in combination with Ciprofloxacin.
Trovafloxacin The therapeutic efficacy of Insulin human can be increased when used in combination with Trovafloxacin.
Nalidixic acid The therapeutic efficacy of Insulin human can be increased when used in combination with Nalidixic acid.
Rosoxacin The therapeutic efficacy of Insulin human can be increased when used in combination with Rosoxacin.
Cinoxacin The therapeutic efficacy of Insulin human can be increased when used in combination with Cinoxacin.
Lomefloxacin The therapeutic efficacy of Insulin human can be increased when used in combination with Lomefloxacin.
Gatifloxacin The therapeutic efficacy of Insulin human can be increased when used in combination with Gatifloxacin.
Norfloxacin The therapeutic efficacy of Insulin human can be increased when used in combination with Norfloxacin.
Levofloxacin The therapeutic efficacy of Insulin human can be increased when used in combination with Levofloxacin.
Gemifloxacin The therapeutic efficacy of Insulin human can be increased when used in combination with Gemifloxacin.
Ofloxacin The therapeutic efficacy of Insulin human can be increased when used in combination with Ofloxacin.
Sparfloxacin The therapeutic efficacy of Insulin human can be increased when used in combination with Sparfloxacin.
Temafloxacin The therapeutic efficacy of Insulin human can be increased when used in combination with Temafloxacin.
Fleroxacin The therapeutic efficacy of Insulin human can be increased when used in combination with Fleroxacin.
Technetium Tc-99m ciprofloxacin The therapeutic efficacy of Insulin human can be increased when used in combination with Technetium Tc-99m ciprofloxacin.
Garenoxacin The therapeutic efficacy of Insulin human can be increased when used in combination with Garenoxacin.
Nemonoxacin The therapeutic efficacy of Insulin human can be increased when used in combination with Nemonoxacin.
Flumequine The therapeutic efficacy of Insulin human can be increased when used in combination with Flumequine.
Enrofloxacin The therapeutic efficacy of Insulin human can be increased when used in combination with Enrofloxacin.
Orbifloxacin The therapeutic efficacy of Insulin human can be increased when used in combination with Orbifloxacin.
Sarafloxacin The therapeutic efficacy of Insulin human can be increased when used in combination with Sarafloxacin.
Difloxacin The therapeutic efficacy of Insulin human can be increased when used in combination with Difloxacin.
Pazufloxacin The therapeutic efficacy of Insulin human can be increased when used in combination with Pazufloxacin.
Prulifloxacin The therapeutic efficacy of Insulin human can be increased when used in combination with Prulifloxacin.
Delafloxacin The therapeutic efficacy of Insulin human can be increased when used in combination with Delafloxacin.
Sitafloxacin The therapeutic efficacy of Insulin human can be increased when used in combination with Sitafloxacin.
Oxolinic acid The therapeutic efficacy of Insulin human can be increased when used in combination with Oxolinic acid.
Rufloxacin The therapeutic efficacy of Insulin human can be increased when used in combination with Rufloxacin.
Pipemidic acid The therapeutic efficacy of Insulin human can be increased when used in combination with Pipemidic acid.
Methyclothiazide The risk or severity of hypoglycemia can be increased when Methyclothiazide is combined with Insulin human.
Chlorthalidone The risk or severity of hypoglycemia can be increased when Chlorthalidone is combined with Insulin human.
Bendroflumethiazide The risk or severity of hypoglycemia can be increased when Bendroflumethiazide is combined with Insulin human.
Metolazone The risk or severity of hypoglycemia can be increased when Metolazone is combined with Insulin human.
Benzthiazide The risk or severity of hypoglycemia can be increased when Benzthiazide is combined with Insulin human.
Hydroflumethiazide The risk or severity of hypoglycemia can be increased when Hydroflumethiazide is combined with Insulin human.
Indapamide The risk or severity of hypoglycemia can be increased when Indapamide is combined with Insulin human.
Chlorothiazide The risk or severity of hypoglycemia can be increased when Chlorothiazide is combined with Insulin human.
Hydrochlorothiazide The risk or severity of hypoglycemia can be increased when Hydrochlorothiazide is combined with Insulin human.
Trichlormethiazide The risk or severity of hypoglycemia can be increased when Trichlormethiazide is combined with Insulin human.
Polythiazide The risk or severity of hypoglycemia can be increased when Polythiazide is combined with Insulin human.
Quinethazone The risk or severity of hypoglycemia can be increased when Quinethazone is combined with Insulin human.
Cyclopenthiazide The risk or severity of hypoglycemia can be increased when Cyclopenthiazide is combined with Insulin human.
Epitizide The therapeutic efficacy of Insulin human can be decreased when used in combination with Epitizide.
Protriptyline Protriptyline may decrease the hypoglycemic activities of Insulin human.
Amoxapine Amoxapine may decrease the hypoglycemic activities of Insulin human.
Trimipramine Trimipramine may decrease the hypoglycemic activities of Insulin human.
Amineptine Amineptine may decrease the hypoglycemic activities of Insulin human.
Dimetacrine Dimetacrine may decrease the hypoglycemic activities of Insulin human.
Butriptyline Butriptyline may decrease the hypoglycemic activities of Insulin human.
Dosulepin Dosulepin may decrease the hypoglycemic activities of Insulin human.
Tianeptine Tianeptine may decrease the hypoglycemic activities of Insulin human.
Oxaprotiline Oxaprotiline may decrease the hypoglycemic activities of Insulin human.
Opipramol Opipramol may decrease the hypoglycemic activities of Insulin human.
Amitriptylinoxide Amitriptylinoxide may decrease the hypoglycemic activities of Insulin human.
Dibenzepin Dibenzepin may decrease the hypoglycemic activities of Insulin human.
Quinupramine Quinupramine may decrease the hypoglycemic activities of Insulin human.
Melitracen Melitracen may decrease the hypoglycemic activities of Insulin human.
Lofepramine Lofepramine may decrease the hypoglycemic activities of Insulin human.
Iprindole Iprindole may decrease the hypoglycemic activities of Insulin human.
Imipramine oxide Imipramine oxide may decrease the hypoglycemic activities of Insulin human.
Nortriptyline Nortriptyline may decrease the hypoglycemic activities of Insulin human.
Desipramine Desipramine may decrease the hypoglycemic activities of Insulin human.
Amitriptyline Amitriptyline may decrease the hypoglycemic activities of Insulin human.
Imipramine Imipramine may decrease the hypoglycemic activities of Insulin human.
Doxepin Doxepin may decrease the hypoglycemic activities of Insulin human.
Clomipramine Clomipramine may decrease the hypoglycemic activities of Insulin human.
Dapagliflozin The risk or severity of hypoglycemia can be increased when Insulin human is combined with Dapagliflozin.
Canagliflozin The risk or severity of hypoglycemia can be increased when Insulin human is combined with Canagliflozin.
Leuprolide The therapeutic efficacy of Insulin human can be decreased when used in combination with Leuprolide.
Goserelin The therapeutic efficacy of Insulin human can be decreased when used in combination with Goserelin.
Nelfinavir The therapeutic efficacy of Insulin human can be decreased when used in combination with Nelfinavir.
Indinavir The therapeutic efficacy of Insulin human can be decreased when used in combination with Indinavir.
Ziprasidone The therapeutic efficacy of Insulin human can be decreased when used in combination with Ziprasidone.
Etonogestrel The therapeutic efficacy of Insulin human can be decreased when used in combination with Etonogestrel.
Desogestrel The therapeutic efficacy of Insulin human can be decreased when used in combination with Desogestrel.
Olanzapine The therapeutic efficacy of Insulin human can be decreased when used in combination with Olanzapine.
Megestrol acetate The therapeutic efficacy of Insulin human can be decreased when used in combination with Megestrol acetate.
Clozapine The therapeutic efficacy of Insulin human can be decreased when used in combination with Clozapine.
Levonorgestrel The therapeutic efficacy of Insulin human can be decreased when used in combination with Levonorgestrel.
Progesterone The therapeutic efficacy of Insulin human can be decreased when used in combination with Progesterone.
Chlorpromazine The therapeutic efficacy of Insulin human can be decreased when used in combination with Chlorpromazine.
Haloperidol The therapeutic efficacy of Insulin human can be decreased when used in combination with Haloperidol.
Ritonavir The therapeutic efficacy of Insulin human can be decreased when used in combination with Ritonavir.
Piperazine The therapeutic efficacy of Insulin human can be decreased when used in combination with Piperazine.
Medroxyprogesterone acetate The therapeutic efficacy of Insulin human can be decreased when used in combination with Medroxyprogesterone acetate.
Niacin The therapeutic efficacy of Insulin human can be decreased when used in combination with Niacin.

Target Protein

Insulin receptor INSR
Insulin-like growth factor 1 receptor IGF1R
Carboxypeptidase E CPE
CCN family member 3 CCN3
Low-density lipoprotein receptor-related protein 2 LRP2
Insulin-like growth factor-binding protein 7 IGFBP7

Referensi & Sumber

Synthesis reference: Humulin is synthesized in a special non-disease-producing laboratory strain of Escherichia coli bacteria that has been genetically altered to produce human insulin.
Artikel (PubMed)
  • PMID: 23512415
    Herrmann BL, Kasser C, Keuthage W, Huptas M, Dette H, Klute A: Comparison of insulin aspart vs. regular human insulin with or without insulin detemir concerning adipozytokines and metabolic effects in patients with type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes. 2013 Apr;121(4):210-3. doi: 10.1055/s-0033-1334905. Epub 2013 Mar 19.
  • PMID: 11118018
    Lepore M, Pampanelli S, Fanelli C, Porcellati F, Bartocci L, Di Vincenzo A, Cordoni C, Costa E, Brunetti P, Bolli GB: Pharmacokinetics and pharmacodynamics of subcutaneous injection of long-acting human insulin analog glargine, NPH insulin, and ultralente human insulin and continuous subcutaneous infusion of insulin lispro. Diabetes. 2000 Dec;49(12):2142-8.
  • PMID: 10841002
    Owens DR, Coates PA, Luzio SD, Tinbergen JP, Kurzhals R: Pharmacokinetics of 125I-labeled insulin glargine (HOE 901) in healthy men: comparison with NPH insulin and the influence of different subcutaneous injection sites. Diabetes Care. 2000 Jun;23(6):813-9.
  • PMID: 14578244
    Danne T, Lupke K, Walte K, Von Schuetz W, Gall MA: Insulin detemir is characterized by a consistent pharmacokinetic profile across age-groups in children, adolescents, and adults with type 1 diabetes. Diabetes Care. 2003 Nov;26(11):3087-92.
  • PMID: 18715209
    Owens DR, Bolli GB: Beyond the era of NPH insulin--long-acting insulin analogs: chemistry, comparative pharmacology, and clinical application. Diabetes Technol Ther. 2008 Oct;10(5):333-49. doi: 10.1089/dia.2008.0023.
  • PMID: 27574374
    Oleck J, Kassam S, Goldman JD: Commentary: Why Was Inhaled Insulin a Failure in the Market? Diabetes Spectr. 2016 Aug;29(3):180-4. doi: 10.2337/diaspect.29.3.180.

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