Peringatan Keamanan

In animal studies, exenatide was associated with fetal deformities of ribs and vertebrae as well as slowed growthLabel. In humans, uncontrolled hyperglycemia can be associated with an up to 25% risk of miscarriageLabel. No human studies in pregnancy have been performed with exenatide and so exenatide should only be prescribed in pregnancy if the benefit to the mother and fetus outweigh the risksLabel. In mice, exenatide is excreted in the milk at a concentration 2.5% of the plasma concentration though this data may not be applicable to humansLabel. The effect of exenatide on breastfed infants is also unknown and so the risk and benefit of breastfeeding while taking exenatide must be weighedLabel. There is no data for the use of exenatide in pediatric patientsLabel. Geriatric patients do not have different results for safety and efficacy of exenatide though caution should still be used in this group as they are at higher risk of renal impairment or other comorbidities that may affect the liklihood of adverse effectsLabel. No dosage adjustments are necessary for patients with creatinine clearance ?50mL/min, though prescribing to patients with creatinine clearance 30-50mL/min should be done cautiouslyLabel. Exenatide is not recommended for patients with creatinine clearance <30mL/minLabel. Hepatic impairment is not expected to affect clearance of exenatide though no studies have been performed to confirm thisLabel.

Exenatide

DB01276

biotech approved investigational

Deskripsi

Exenatide is a glucagon-like peptide-1 (GLP-1) analogL42690. It activates the GLP-1 receptor and increases insulin secretion, decreases glucagon secretion, and slows gastric emptying to improve glycemic controlL42690. Exenatide was given FDA approval on April 28, 2005L6106. It is available as immediate- and extended-release formulations.L42685,L42690 Bydureon, the brand name product of extended-release exenatide in an injectable suspension, was discontinued in 2021. Bydureon BCise, an auto-injector extended-release formulation, remains available.L42700

Struktur Molekul 2D

Struktur tidak tersedia

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) 2.4 hours[Label]
Volume Distribusi 28.3L[Label].
Klirens (Clearance) 9.1 L/hour[Label].

Absorpsi

Exenatide reaches a peak plasma concentration in 2.1 hoursLabel. Because exenatide is administerd subcutaneously, the bioavailability is 1A177706.

Metabolisme

Exenatide is filtered through the glomerulus before being degraded to smaller peptides and amino acids by dipeptidyl peptidase-4, metalloproteases, endopeptidase 24-11, amino proteases, and serine proteasesLabel,A177718. It is currently believed that the metalloproteases are responsible for most of the degradation of exenatideA177718. Exenatide is metabolised to small peptides <3 amino acids in length by enzymes in the kidneyA177712.

Rute Eliminasi

Exenatide is mainly eliminated by glomerular filtration followed by proteolysis before finally being eliminated in the urineLabel,A177712.

Interaksi Makanan

1 Data
  • 1. Take before a meal. Inject subcutaneously within 60 minutes before morning and evening meals.

Interaksi Obat

648 Data
Pegvisomant The risk or severity of hypoglycemia can be increased when Pegvisomant is combined with Exenatide.
Diethylstilbestrol Exenatide can cause a decrease in the absorption of Diethylstilbestrol resulting in a reduced serum concentration and potentially a decrease in efficacy.
Etonogestrel Exenatide can cause a decrease in the absorption of Etonogestrel resulting in a reduced serum concentration and potentially a decrease in efficacy.
Progesterone Exenatide can cause a decrease in the absorption of Progesterone resulting in a reduced serum concentration and potentially a decrease in efficacy.
Mestranol Exenatide can cause a decrease in the absorption of Mestranol resulting in a reduced serum concentration and potentially a decrease in efficacy.
Estrone sulfate Exenatide can cause a decrease in the absorption of Estrone sulfate resulting in a reduced serum concentration and potentially a decrease in efficacy.
Octylphenoxy polyethoxyethanol Exenatide can cause a decrease in the absorption of Octylphenoxy polyethoxyethanol resulting in a reduced serum concentration and potentially a decrease in efficacy.
Trestolone Exenatide can cause a decrease in the absorption of Trestolone resulting in a reduced serum concentration and potentially a decrease in efficacy.
Norelgestromin Exenatide can cause a decrease in the absorption of Norelgestromin resulting in a reduced serum concentration and potentially a decrease in efficacy.
Hydroxyprogesterone caproate Exenatide can cause a decrease in the absorption of Hydroxyprogesterone caproate resulting in a reduced serum concentration and potentially a decrease in efficacy.
Ulipristal Exenatide can cause a decrease in the absorption of Ulipristal resulting in a reduced serum concentration and potentially a decrease in efficacy.
Cloprostenol Exenatide can cause a decrease in the absorption of Cloprostenol resulting in a reduced serum concentration and potentially a decrease in efficacy.
Nomegestrol Exenatide can cause a decrease in the absorption of Nomegestrol resulting in a reduced serum concentration and potentially a decrease in efficacy.
Gossypol Exenatide can cause a decrease in the absorption of Gossypol resulting in a reduced serum concentration and potentially a decrease in efficacy.
Etynodiol Exenatide can cause a decrease in the absorption of Etynodiol resulting in a reduced serum concentration and potentially a decrease in efficacy.
Testosterone enanthate Exenatide can cause a decrease in the absorption of Testosterone enanthate resulting in a reduced serum concentration and potentially a decrease in efficacy.
Estradiol benzoate Exenatide can cause a decrease in the absorption of Estradiol benzoate resulting in a reduced serum concentration and potentially a decrease in efficacy.
Estradiol cypionate Exenatide can cause a decrease in the absorption of Estradiol cypionate resulting in a reduced serum concentration and potentially a decrease in efficacy.
Estradiol valerate Exenatide can cause a decrease in the absorption of Estradiol valerate resulting in a reduced serum concentration and potentially a decrease in efficacy.
Norethindrone enanthate Exenatide can cause a decrease in the absorption of Norethindrone enanthate resulting in a reduced serum concentration and potentially a decrease in efficacy.
Dicoumarol Exenatide can cause an increase in the absorption of Dicoumarol resulting in an increased serum concentration and potentially a worsening of adverse effects.
Phenindione Exenatide can cause an increase in the absorption of Phenindione resulting in an increased serum concentration and potentially a worsening of adverse effects.
Warfarin Exenatide can cause an increase in the absorption of Warfarin resulting in an increased serum concentration and potentially a worsening of adverse effects.
Phenprocoumon Exenatide can cause an increase in the absorption of Phenprocoumon resulting in an increased serum concentration and potentially a worsening of adverse effects.
Acenocoumarol Exenatide can cause an increase in the absorption of Acenocoumarol resulting in an increased serum concentration and potentially a worsening of adverse effects.
4-hydroxycoumarin Exenatide can cause an increase in the absorption of 4-hydroxycoumarin resulting in an increased serum concentration and potentially a worsening of adverse effects.
Coumarin Exenatide can cause an increase in the absorption of Coumarin resulting in an increased serum concentration and potentially a worsening of adverse effects.
(R)-warfarin Exenatide can cause an increase in the absorption of (R)-warfarin resulting in an increased serum concentration and potentially a worsening of adverse effects.
Ethyl biscoumacetate Exenatide can cause an increase in the absorption of Ethyl biscoumacetate resulting in an increased serum concentration and potentially a worsening of adverse effects.
Fluindione Exenatide can cause an increase in the absorption of Fluindione resulting in an increased serum concentration and potentially a worsening of adverse effects.
Clorindione Exenatide can cause an increase in the absorption of Clorindione resulting in an increased serum concentration and potentially a worsening of adverse effects.
Diphenadione Exenatide can cause an increase in the absorption of Diphenadione resulting in an increased serum concentration and potentially a worsening of adverse effects.
Tioclomarol Exenatide can cause an increase in the absorption of Tioclomarol resulting in an increased serum concentration and potentially a worsening of adverse effects.
(S)-Warfarin Exenatide can cause an increase in the absorption of (S)-Warfarin resulting in an increased serum concentration and potentially a worsening of adverse effects.
Lipoic acid The risk or severity of hypoglycemia can be increased when Lipoic acid is combined with Exenatide.
Moxifloxacin The therapeutic efficacy of Exenatide can be increased when used in combination with Moxifloxacin.
Grepafloxacin The therapeutic efficacy of Exenatide can be increased when used in combination with Grepafloxacin.
Enoxacin The therapeutic efficacy of Exenatide can be increased when used in combination with Enoxacin.
Pefloxacin The therapeutic efficacy of Exenatide can be increased when used in combination with Pefloxacin.
Ciprofloxacin The therapeutic efficacy of Exenatide can be increased when used in combination with Ciprofloxacin.
Trovafloxacin The therapeutic efficacy of Exenatide can be increased when used in combination with Trovafloxacin.
Nalidixic acid The therapeutic efficacy of Exenatide can be increased when used in combination with Nalidixic acid.
Rosoxacin The therapeutic efficacy of Exenatide can be increased when used in combination with Rosoxacin.
Cinoxacin The therapeutic efficacy of Exenatide can be increased when used in combination with Cinoxacin.
Lomefloxacin The therapeutic efficacy of Exenatide can be increased when used in combination with Lomefloxacin.
Gatifloxacin The therapeutic efficacy of Exenatide can be increased when used in combination with Gatifloxacin.
Norfloxacin The therapeutic efficacy of Exenatide can be increased when used in combination with Norfloxacin.
Levofloxacin The therapeutic efficacy of Exenatide can be increased when used in combination with Levofloxacin.
Gemifloxacin The therapeutic efficacy of Exenatide can be increased when used in combination with Gemifloxacin.
Ofloxacin The therapeutic efficacy of Exenatide can be increased when used in combination with Ofloxacin.
Sparfloxacin The therapeutic efficacy of Exenatide can be increased when used in combination with Sparfloxacin.
Temafloxacin The therapeutic efficacy of Exenatide can be increased when used in combination with Temafloxacin.
Fleroxacin The therapeutic efficacy of Exenatide can be increased when used in combination with Fleroxacin.
Technetium Tc-99m ciprofloxacin The therapeutic efficacy of Exenatide can be increased when used in combination with Technetium Tc-99m ciprofloxacin.
Garenoxacin The therapeutic efficacy of Exenatide can be increased when used in combination with Garenoxacin.
Nemonoxacin The therapeutic efficacy of Exenatide can be increased when used in combination with Nemonoxacin.
Flumequine The therapeutic efficacy of Exenatide can be increased when used in combination with Flumequine.
Enrofloxacin The therapeutic efficacy of Exenatide can be increased when used in combination with Enrofloxacin.
Orbifloxacin The therapeutic efficacy of Exenatide can be increased when used in combination with Orbifloxacin.
Sarafloxacin The therapeutic efficacy of Exenatide can be increased when used in combination with Sarafloxacin.
Difloxacin The therapeutic efficacy of Exenatide can be increased when used in combination with Difloxacin.
Pazufloxacin The therapeutic efficacy of Exenatide can be increased when used in combination with Pazufloxacin.
Prulifloxacin The therapeutic efficacy of Exenatide can be increased when used in combination with Prulifloxacin.
Delafloxacin The therapeutic efficacy of Exenatide can be increased when used in combination with Delafloxacin.
Sitafloxacin The therapeutic efficacy of Exenatide can be increased when used in combination with Sitafloxacin.
Oxolinic acid The therapeutic efficacy of Exenatide can be increased when used in combination with Oxolinic acid.
Rufloxacin The therapeutic efficacy of Exenatide can be increased when used in combination with Rufloxacin.
Pipemidic acid The therapeutic efficacy of Exenatide can be increased when used in combination with Pipemidic acid.
Methyclothiazide The therapeutic efficacy of Exenatide can be decreased when used in combination with Methyclothiazide.
Chlorthalidone The therapeutic efficacy of Exenatide can be decreased when used in combination with Chlorthalidone.
Bendroflumethiazide The therapeutic efficacy of Exenatide can be decreased when used in combination with Bendroflumethiazide.
Metolazone The therapeutic efficacy of Exenatide can be decreased when used in combination with Metolazone.
Benzthiazide The therapeutic efficacy of Exenatide can be decreased when used in combination with Benzthiazide.
Hydroflumethiazide The therapeutic efficacy of Exenatide can be decreased when used in combination with Hydroflumethiazide.
Indapamide The therapeutic efficacy of Exenatide can be decreased when used in combination with Indapamide.
Chlorothiazide The therapeutic efficacy of Exenatide can be decreased when used in combination with Chlorothiazide.
Hydrochlorothiazide The therapeutic efficacy of Exenatide can be decreased when used in combination with Hydrochlorothiazide.
Trichlormethiazide The therapeutic efficacy of Exenatide can be decreased when used in combination with Trichlormethiazide.
Polythiazide The therapeutic efficacy of Exenatide can be decreased when used in combination with Polythiazide.
Quinethazone The therapeutic efficacy of Exenatide can be decreased when used in combination with Quinethazone.
Cyclopenthiazide The therapeutic efficacy of Exenatide can be decreased when used in combination with Cyclopenthiazide.
Epitizide The therapeutic efficacy of Exenatide can be decreased when used in combination with Epitizide.
Amitriptyline Amitriptyline may decrease the hypoglycemic activities of Exenatide.
Protriptyline Protriptyline may decrease the hypoglycemic activities of Exenatide.
Imipramine Imipramine may decrease the hypoglycemic activities of Exenatide.
Nortriptyline Nortriptyline may decrease the hypoglycemic activities of Exenatide.
Amoxapine Amoxapine may decrease the hypoglycemic activities of Exenatide.
Trimipramine Trimipramine may decrease the hypoglycemic activities of Exenatide.
Doxepin Doxepin may decrease the hypoglycemic activities of Exenatide.
Desipramine Desipramine may decrease the hypoglycemic activities of Exenatide.
Clomipramine Clomipramine may decrease the hypoglycemic activities of Exenatide.
Amineptine Amineptine may decrease the hypoglycemic activities of Exenatide.
Dimetacrine Dimetacrine may decrease the hypoglycemic activities of Exenatide.
Butriptyline Butriptyline may decrease the hypoglycemic activities of Exenatide.
Dosulepin Dosulepin may decrease the hypoglycemic activities of Exenatide.
Tianeptine Tianeptine may decrease the hypoglycemic activities of Exenatide.
Oxaprotiline Oxaprotiline may decrease the hypoglycemic activities of Exenatide.
Opipramol Opipramol may decrease the hypoglycemic activities of Exenatide.
Amitriptylinoxide Amitriptylinoxide may decrease the hypoglycemic activities of Exenatide.
Dibenzepin Dibenzepin may decrease the hypoglycemic activities of Exenatide.

Target Protein

Glucagon-like peptide 1 receptor GLP1R

Referensi & Sumber

Synthesis reference: Matthieu Giraud, Anne-Sophie Droz, Stephane Varray, El Djouhar Rekai, Marie-Helene Brichard, Daniel Latassa, Christine Devijver, Pascal Gilles, Jeanne-Marie Cauvin, Fernando Albericio, Marta Paradis Bas, "PROCESS FOR THE PRODUCTION OF EXENATIDE AND OF AN EXENATIDE ANALOGUE." U.S. Patent US20110046349, issued February 24, 2011.
Artikel (PubMed)
  • PMID: 22338110
    Gao W, Jusko WJ: Target-mediated pharmacokinetic and pharmacodynamic model of exendin-4 in rats, monkeys, and humans. Drug Metab Dispos. 2012 May;40(5):990-7. doi: 10.1124/dmd.111.042291. Epub 2012 Feb 15.
  • PMID: 16724926
    Copley K, McCowen K, Hiles R, Nielsen LL, Young A, Parkes DG: Investigation of exenatide elimination and its in vivo and in vitro degradation. Curr Drug Metab. 2006 May;7(4):367-74.
  • PMID: 25723538
    Liao S, Liang Y, Zhang Z, Li J, Wang J, Wang X, Dou G, Zhang Z, Liu K: In vitro metabolic stability of exendin-4: pharmacokinetics and identification of cleavage products. PLoS One. 2015 Feb 27;10(2):e0116805. doi: 10.1371/journal.pone.0116805. eCollection 2015.

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