Peringatan Keamanan

LD50 >1 g/kg (rat) (W. Grell)

Repaglinide

DB00912

small molecule approved investigational

Deskripsi

Repaglinide is an oral antihyperglycemic agent used for the treatment of non-insulin-dependent diabetes mellitus (NIDDM). It belongs to the meglitinide class of short-acting insulin secretagogues, which act by binding to ? cells of the pancreas to stimulate insulin release. Repaglinide induces an early insulin response to meals decreasing postprandial blood glucose levels. It should only be taken with meals and meal-time doses should be skipped with any skipped meal. Approximately one month of therapy is required before a decrease in fasting blood glucose is seen. Meglitnides may have a neutral effect on weight or cause a slight increase in weight. The average weight gain caused by meglitinides appears to be lower than that caused by sulfonylureas and insulin and appears to occur only in those naïve to oral antidiabetic agents. Due to their mechanism of action, meglitinides may cause hypoglycemia although the risk is thought to be lower than that of sulfonylureas since their action is dependent on the presence of glucose. In addition to reducing postprandial and fasting blood glucose, meglitnides have been shown to decrease glycosylated hemoglobin (HbA1c) levels, which are reflective of the last 8-10 weeks of glucose control. Meglitinides appear to be more effective at lowering postprandial blood glucose than metformin, sulfonylureas and thiazolidinediones. Repaglinide is extensively metabolized in the liver and excreted in bile. Repaglinide metabolites do not possess appreciable hypoglycemic activity. Approximately 90% of a single orally administered dose is eliminated in feces and 8% in urine.

Struktur Molekul 2D

Berat 452.5857
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) 1 hour
Volume Distribusi 31 L following IV administration in healthy individuals
Klirens (Clearance) 33-38 L/hour following IV administration

Absorpsi

Rapidly and completely absorbed following oral administration. Peak plasma concentrations are observed within 1 hour (range 0.5-1.4 hours). The absolute bioavailability is approximately 56%. Maximal biological effect is observed within 3-3.5 hours and plasma insulin levels remain elevated for 4-6 hours. When a single 2 mg dose of repaglinide is given to healthy subjects, the area under the curve (AUC) is 18.0 - 18.7 (ng/mL/h)^3.

Metabolisme

Repaglinide is rapidly metabolized via oxidation and dealkylation by cytochrome P450 3A4 and 2C9 to form the major dicarboxylic acid derivative (M2). Further oxidation produces the aromatic amine derivative (M1). Glucuronidation of the carboxylic acid group of repaglinide yields an acyl glucuronide (M7). Several other unidentified metabolites have been detected. Repaglinide metabolites to not possess appreciable hypoglycemic activity.

Rute Eliminasi

90% eliminated in feces (<2% as unchanged drug), 8% in urine (0.1% as unchanged drug)

Interaksi Makanan

1 Data
  • 1. Take before a meal. Repaglinide should be taken before each meal of the day.

Interaksi Obat

939 Data
Pegvisomant The risk or severity of hypoglycemia can be increased when Pegvisomant is combined with Repaglinide.
Reserpine Reserpine may decrease the excretion rate of Repaglinide which could result in a higher serum level.
Progesterone Progesterone may decrease the excretion rate of Repaglinide which could result in a higher serum level.
Chlorpromazine Chlorpromazine may decrease the excretion rate of Repaglinide which could result in a higher serum level.
Cimetidine Cimetidine may decrease the excretion rate of Repaglinide which could result in a higher serum level.
Bosentan Bosentan may decrease the excretion rate of Repaglinide which could result in a higher serum level.
Tamoxifen Tamoxifen may decrease the excretion rate of Repaglinide which could result in a higher serum level.
Ethinylestradiol Ethinylestradiol may decrease the excretion rate of Repaglinide which could result in a higher serum level.
Glyburide Glyburide may decrease the excretion rate of Repaglinide which could result in a higher serum level.
Ursodeoxycholic acid Ursodeoxycholic acid may decrease the excretion rate of Repaglinide which could result in a higher serum level.
Cholic Acid Cholic Acid may decrease the excretion rate of Repaglinide which could result in a higher serum level.
Fusidic acid Fusidic acid may decrease the excretion rate of Repaglinide which could result in a higher serum level.
Simeprevir Simeprevir may decrease the excretion rate of Repaglinide which could result in a higher serum level.
Lenvatinib Lenvatinib may decrease the excretion rate of Repaglinide which could result in a higher serum level.
Letermovir The metabolism of Repaglinide can be decreased when combined with Letermovir.
Valinomycin Valinomycin may decrease the excretion rate of Repaglinide which could result in a higher serum level.
Quinidine Quinidine may decrease the excretion rate of Repaglinide which could result in a higher serum level.
Olmesartan Olmesartan may decrease the excretion rate of Repaglinide which could result in a higher serum level.
Pralsetinib Pralsetinib may decrease the excretion rate of Repaglinide which could result in a higher serum level.
Cyclosporine The serum concentration of Repaglinide can be increased when it is combined with Cyclosporine.
Erythromycin The serum concentration of Repaglinide can be increased when it is combined with Erythromycin.
Sirolimus The serum concentration of Repaglinide can be increased when it is combined with Sirolimus.
Dirithromycin The serum concentration of Repaglinide can be increased when it is combined with Dirithromycin.
Telithromycin The serum concentration of Repaglinide can be increased when it is combined with Telithromycin.
Candicidin The serum concentration of Repaglinide can be increased when it is combined with Candicidin.
Clarithromycin The serum concentration of Repaglinide can be increased when it is combined with Clarithromycin.
Josamycin The serum concentration of Repaglinide can be increased when it is combined with Josamycin.
Everolimus The serum concentration of Repaglinide can be increased when it is combined with Everolimus.
Epothilone D The serum concentration of Repaglinide can be increased when it is combined with Epothilone D.
Patupilone The serum concentration of Repaglinide can be increased when it is combined with Patupilone.
6-Deoxyerythronolide B The serum concentration of Repaglinide can be increased when it is combined with 6-Deoxyerythronolide B.
Ixabepilone The serum concentration of Repaglinide can be increased when it is combined with Ixabepilone.
KOS-1584 The serum concentration of Repaglinide can be increased when it is combined with KOS-1584.
Ridaforolimus The serum concentration of Repaglinide can be increased when it is combined with Ridaforolimus.
Temsirolimus The serum concentration of Repaglinide can be increased when it is combined with Temsirolimus.
AVE9633 The serum concentration of Repaglinide can be increased when it is combined with AVE9633.
Coltuximab ravtansine The serum concentration of Repaglinide can be increased when it is combined with Coltuximab ravtansine.
Cethromycin The serum concentration of Repaglinide can be increased when it is combined with Cethromycin.
Mitemcinal The serum concentration of Repaglinide can be increased when it is combined with Mitemcinal.
Brefeldin A The serum concentration of Repaglinide can be increased when it is combined with Brefeldin A.
Solithromycin The serum concentration of Repaglinide can be increased when it is combined with Solithromycin.
Kitasamycin The serum concentration of Repaglinide can be increased when it is combined with Kitasamycin.
Carbomycin The serum concentration of Repaglinide can be increased when it is combined with Carbomycin.
Doramectin The serum concentration of Repaglinide can be increased when it is combined with Doramectin.
Eprinomectin The serum concentration of Repaglinide can be increased when it is combined with Eprinomectin.
Oleandomycin The serum concentration of Repaglinide can be increased when it is combined with Oleandomycin.
Selamectin The serum concentration of Repaglinide can be increased when it is combined with Selamectin.
Tildipirosin The serum concentration of Repaglinide can be increased when it is combined with Tildipirosin.
Tilmicosin The serum concentration of Repaglinide can be increased when it is combined with Tilmicosin.
Tylosin The serum concentration of Repaglinide can be increased when it is combined with Tylosin.
Tylvalosin The serum concentration of Repaglinide can be increased when it is combined with Tylvalosin.
Bryostatin 1 The serum concentration of Repaglinide can be increased when it is combined with Bryostatin 1.
Lorvotuzumab mertansine The serum concentration of Repaglinide can be increased when it is combined with Lorvotuzumab mertansine.
Epofolate The serum concentration of Repaglinide can be increased when it is combined with Epofolate.
Sagopilone The serum concentration of Repaglinide can be increased when it is combined with Sagopilone.
Troleandomycin The serum concentration of Repaglinide can be increased when it is combined with Troleandomycin.
Miocamycin The serum concentration of Repaglinide can be increased when it is combined with Miocamycin.
Flurithromycin The serum concentration of Repaglinide can be increased when it is combined with Flurithromycin.
Rokitamycin The serum concentration of Repaglinide can be increased when it is combined with Rokitamycin.
Midecamycin The serum concentration of Repaglinide can be increased when it is combined with Midecamycin.
Clindamycin The serum concentration of Repaglinide can be increased when it is combined with Clindamycin.
Mepartricin The serum concentration of Repaglinide can be increased when it is combined with Mepartricin.
Mifepristone The serum concentration of Repaglinide can be increased when it is combined with Mifepristone.
Trimethoprim The serum concentration of Repaglinide can be increased when it is combined with Trimethoprim.
Deferasirox The serum concentration of Repaglinide can be increased when it is combined with Deferasirox.
Leflunomide The serum concentration of Repaglinide can be increased when it is combined with Leflunomide.
Teriflunomide The serum concentration of Repaglinide can be increased when it is combined with Teriflunomide.
Rifampin The serum concentration of Repaglinide can be decreased when it is combined with Rifampicin.
Lipoic acid The risk or severity of hypoglycemia can be increased when Lipoic acid is combined with Repaglinide.
Moxifloxacin The therapeutic efficacy of Repaglinide can be increased when used in combination with Moxifloxacin.
Grepafloxacin The therapeutic efficacy of Repaglinide can be increased when used in combination with Grepafloxacin.
Enoxacin The therapeutic efficacy of Repaglinide can be increased when used in combination with Enoxacin.
Pefloxacin The therapeutic efficacy of Repaglinide can be increased when used in combination with Pefloxacin.
Ciprofloxacin The therapeutic efficacy of Repaglinide can be increased when used in combination with Ciprofloxacin.
Trovafloxacin The therapeutic efficacy of Repaglinide can be increased when used in combination with Trovafloxacin.
Nalidixic acid The therapeutic efficacy of Repaglinide can be increased when used in combination with Nalidixic acid.
Rosoxacin The therapeutic efficacy of Repaglinide can be increased when used in combination with Rosoxacin.
Cinoxacin The therapeutic efficacy of Repaglinide can be increased when used in combination with Cinoxacin.
Lomefloxacin The therapeutic efficacy of Repaglinide can be increased when used in combination with Lomefloxacin.
Gatifloxacin The therapeutic efficacy of Repaglinide can be increased when used in combination with Gatifloxacin.
Norfloxacin The therapeutic efficacy of Repaglinide can be increased when used in combination with Norfloxacin.
Levofloxacin The therapeutic efficacy of Repaglinide can be increased when used in combination with Levofloxacin.
Gemifloxacin The therapeutic efficacy of Repaglinide can be increased when used in combination with Gemifloxacin.
Ofloxacin The therapeutic efficacy of Repaglinide can be increased when used in combination with Ofloxacin.
Sparfloxacin The therapeutic efficacy of Repaglinide can be increased when used in combination with Sparfloxacin.
Temafloxacin The therapeutic efficacy of Repaglinide can be increased when used in combination with Temafloxacin.
Fleroxacin The therapeutic efficacy of Repaglinide can be increased when used in combination with Fleroxacin.
Technetium Tc-99m ciprofloxacin The therapeutic efficacy of Repaglinide can be increased when used in combination with Technetium Tc-99m ciprofloxacin.
Garenoxacin The therapeutic efficacy of Repaglinide can be increased when used in combination with Garenoxacin.
Nemonoxacin The therapeutic efficacy of Repaglinide can be increased when used in combination with Nemonoxacin.
Flumequine The therapeutic efficacy of Repaglinide can be increased when used in combination with Flumequine.
Enrofloxacin The therapeutic efficacy of Repaglinide can be increased when used in combination with Enrofloxacin.
Orbifloxacin The therapeutic efficacy of Repaglinide can be increased when used in combination with Orbifloxacin.
Sarafloxacin The therapeutic efficacy of Repaglinide can be increased when used in combination with Sarafloxacin.
Difloxacin The therapeutic efficacy of Repaglinide can be increased when used in combination with Difloxacin.
Pazufloxacin The therapeutic efficacy of Repaglinide can be increased when used in combination with Pazufloxacin.
Prulifloxacin The therapeutic efficacy of Repaglinide can be increased when used in combination with Prulifloxacin.
Delafloxacin The therapeutic efficacy of Repaglinide can be increased when used in combination with Delafloxacin.
Sitafloxacin The therapeutic efficacy of Repaglinide can be increased when used in combination with Sitafloxacin.
Oxolinic acid The therapeutic efficacy of Repaglinide can be increased when used in combination with Oxolinic acid.

Target Protein

ATP-binding cassette sub-family C member 9 ABCC9
ATP-binding cassette sub-family C member 8 ABCC8
Histamine H1 receptor HRH1
Peroxisome proliferator-activated receptor gamma PPARG

Referensi & Sumber

Synthesis reference: Manne Reddy, "Polymorphic forms of (S)-Repaglinide and the processes for preparation thereof." U.S. Patent US20040102477, issued May 27, 2004.
Artikel (PubMed)
  • PMID: 11060717
    Massi-Benedetti M, Damsbo P: Pharmacology and clinical experience with repaglinide. Expert Opin Investig Drugs. 2000 Apr;9(4):885-98.

Contoh Produk & Brand

Produk: 188 • International brands: 2
Produk
  • Act Repaglinide
    Tablet • 0.5 mg • Oral • Canada • Approved
  • Act Repaglinide
    Tablet • 1 mg • Oral • Canada • Approved
  • Act Repaglinide
    Tablet • 2 mg • Oral • Canada • Approved
  • Apo-repaglinide
    Tablet • 0.5 mg • Oral • Canada • Generic • Approved
  • Apo-repaglinide
    Tablet • 1.0 mg • Oral • Canada • Generic • Approved
  • Apo-repaglinide
    Tablet • 2.0 mg • Oral • Canada • Generic • Approved
  • Auro-repaglinide
    Tablet • 0.5 mg • Oral • Canada • Generic • Approved
  • Auro-repaglinide
    Tablet • 1 mg • Oral • Canada • Generic • Approved
Menampilkan 8 dari 188 produk.
International Brands
  • GlucoNorm — Novo Nordisk
  • Surepost

Sekuens Gen/Protein (FASTA)

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