Peringatan Keamanan

The oral LD₅₀ values were 230 and <200 mg/kg for male and female mice, <300 and 150 mg/kg for male and female rats, and <225 and 225 for male and female rabbits.^L40699 In mice, rats, and rabbits, intravenous LD₅₀ values had a range of 15.0-48.5 mg/kg and subcutaneous LD₅₀ values were in the range of 157-1150 mg/kg.^L40704

Nalmefene was well tolerated and showed no serious toxicity during experimental administration to healthy individuals, even when given at 15 times the highest recommended dose. In a small number of subjects, at doses exceeding the recommended nalmefene injection dose, nalmefene produced symptoms suggestive of reversal of endogenous opioids, such as nausea, chills, myalgia, dysphoria, abdominal cramps, and joint pain. These symptoms can also arise in other narcotic antagonist drugs and they are usually transient in nature and occur at a very low frequency.^L40684

Large doses of nalmefene have been used in studies. For example, one study used doses of nalmefene up to 90 mg/day for 16 weeks in patients diagnosed with pathological gambling. In a study in patients with interstitial cystitis, 20 patients received 108 mg/day of nalmefene for more than two years. Intake of a single dose of 450 mg nalmefene has been reported without changes in blood pressure, heart rate, respiration rate, or body temperature. There was no unusual pattern of adverse reactions, but the experience is limited. Management of an overdose should be observational and symptomatic.^L1024

Nalmefene

DB06230

small molecule approved investigational withdrawn

Deskripsi

Nalmefene, a 6-methylene analogue of naltrexone, is an opioid receptor antagonist.^L40684 It acts as an antagonist at the mu (?)-opioid and delta (?)-opioid receptors and a partial agonist at the kappa (?)-opioid receptor.^L1024

In Europe, nalmefene oral tablets are used to reduce alcohol consumption in adults with alcohol dependence.^L1024 Nalmefene was approved in the United States in 1995 as an antidote for opioid overdose.^A245839 Nalmefene injection is used to manage known or suspected opioid overdose. It is used for complete or partial reversal of opioid drug effects, including respiratory depression, induced by either natural or synthetic opioids.^L40684 The nasal spray formulation of nalmefene was approved by the FDA in May 2023.^L46511

Struktur Molekul 2D

Berat 339.435

Wujud solid

Peta Jejaring Molekuler

Obat Target Gen Interaksi Enzim Transporter Carrier

Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

1. Pendahuluan & Konsep

Fitur visualisasi ini dikembangkan menggunakan pendekatan Graph Theory untuk memetakan hubungan polifarmasi dan molekuler. Entitas (Obat, Target, Gen) direpresentasikan sebagai Simpul (Nodes), sedangkan hubungan biologisnya sebagai Sisi (Edges).

2. Sumber Data (Validasi)

Data Obat: Diekstraksi dari elemen drugbank-id dan name pada skema XML DrugBank.
Target Protein: Diambil dari elemen targets/target yang memuat polipeptida sasaran.
Genetik: Disinkronisasi dari sub-elemen gene-name dan varian snp-effects.
Genetik: Jumlah titik node dibatasi pada maksimal 10 (Slice=10) interaksi untuk menghindari tumpukan data.

3. Algoritma Visualisasi

Tata letak grafik menggunakan algoritma Force-Directed Graph (Barnes-Hut). Model fisika ini menerapkan gaya tolak-menolak antar simpul (Gravitasi: -3000) agar tidak tumpang tindih, serta gaya pegas (Spring: 0.04) pada garis penghubung untuk fleksibilitas interaksi.

4. Legenda Visual

Obat Utama (Pusat Analisis)

Target Protein (Mekanisme)

Gen (Faktor Genetik)

Metode ini mendukung analisis Precision Medicine dan evaluasi risiko Drug-Drug Interaction (DDI).

Profil Farmakokinetik

Waktu Paruh (Half-Life) The terminal half-life is approximately 12.5 hours following oral administration.[L1024] After intravenous administration of 1 mg nalmefene to healthy adult male subjects, plasma concentrations declined biexponentially with redistribution and a terminal elimination half-life of 41 ± 34 minutes and 10.8 ± 5.2 hours, respectively.[L40684]

Volume Distribusi Following a 1 mg parenteral dose, nalmefene was rapidly distributed. The apparent volumes of distribution centrally (V<sub>c</sub>) and at steady-state (V<sub>dss</sub>) are 3.9 ± 1.1 L/kg and 8.6 ± 1.7 L/kg, respectively.[L40684] Nalmefene readily crosses the blood-brain barrier.[L1024]

Klirens (Clearance) The oral clearance of nalmefene (CL/F) was estimated as 169 L/h.[L1024] Following intravenous administration of 1 mg nalmefene, the systemic clearance of nalmefene was 0.8 ± 0.2 L/hr/kg and the renal clearance was 0.08 ± 0.04 L/hr/kg.[L40684]

Absorpsi

Nalmefene is rapidly absorbed after a single oral administration of 18.06 mg with an absolute oral bioavailability of 41%. The C_max was 16.5 ng/mL and T_max was approximately 1.5 hours. The exposure (AUC) was 131 ng x h/mL. High-fat meal increased the AUC by 30% and C_max by 50% and delayed T_max by 30 min; however, this is unlikely of clinical significance.^L1024 Nalmefene exhibits dose-proportional pharmacokinetics following intravenous administration of 0.5 mg to 2 mg. T_max was 2.3 ± 1.1 hours following intramuscular administration and 1.5 ± 1.2 hours following subcutaneous administration. Therapeutic plasma concentrations are likely to be reached within 5 to 15 minutes after a 1 mg dose in an emergency. There is variability in the speed of absorption for intramuscular and subcutaneous dosing.^L40684

Metabolisme

Nalmefene is extensively metabolized by the liver, primarily by glucuronide conjugation mainly mediated by UGT2B7 and UGT1A3 and UGT1A8 to a lesser extent. The major metabolite is pharmacologically inactive nalmefene 3-O-glucuronide.^L1024 Nalmefene is also metabolized to trace amounts of an N-dealkylated metabolite, which has minimal pharmacological activity.^L40684 Nalmefene can undergo dealkylation mediated by CYP3A4/5 to form nornalmefene. Nornalmefene can be further converted to nornalmefene 3-O-glucuronide and nornalmefene 3-sulfate, which are generally inactive metabolites.^L1024 Nalmefene can also undergo CYP3A4/5-mediated sulfation to form nalmefene 3-O-sulfate, which retains some pharmacological activity. However, nalmefene 3-O-sulfate is present in the circulation in less than 10% of that of nalmefene; thus, it is unlikely to be a major contributor to the pharmacological activity of nalmefene.^L1024 The plasma concentration-time profile in some subjects suggests that nalmefene undergoes enterohepatic recycling.^L40684

Rute Eliminasi

Renal excretion is the main route of elimination for nalmefene and its metabolites. About 54% of the total dose is excreted in the urine as nalmefene 3-O-glucuronide. Less than 3% of the dose is excreted as nalmefene or other metabolites ^L1024. About 17% of the dose is excreted in the feces.^L40684

Interaksi Makanan

1 Data

1. Take with or without food. High-fat food increases the AUC by 30% and Cmax by 50% and delays Tmax by 30 min, but this is unlikely of clinical relevance.

Interaksi Obat

782 Data

Methylnaltrexone	Nalmefene may increase the opioid antagonism activities of Methylnaltrexone.
Naloxegol	Nalmefene may increase the opioid antagonism activities of Naloxegol.
Cyclosporine	Cyclosporine may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Icosapent	Icosapent may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Cefotiam	Cefotiam may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Mesalazine	Mesalazine may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Cefmenoxime	Cefmenoxime may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Cefmetazole	Cefmetazole may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Pamidronic acid	Pamidronic acid may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Tenofovir disoproxil	Tenofovir disoproxil may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Cidofovir	Cidofovir may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Cefpiramide	Cefpiramide may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Ceftazidime	Ceftazidime may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Loracarbef	Loracarbef may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Cefalotin	Cefalotin may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Nabumetone	Nabumetone may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Ketorolac	Ketorolac may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Tenoxicam	Tenoxicam may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Celecoxib	Celecoxib may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Cefotaxime	Cefotaxime may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Tolmetin	Tolmetin may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Foscarnet	Foscarnet may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Rofecoxib	Rofecoxib may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Piroxicam	Piroxicam may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Methotrexate	Methotrexate may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Cephalexin	Cephalexin may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Fenoprofen	Fenoprofen may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Valaciclovir	Valaciclovir may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Valdecoxib	Valdecoxib may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Diclofenac	Diclofenac may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Sulindac	Sulindac may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Bacitracin	Bacitracin may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Amphotericin B	Amphotericin B may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Cephaloglycin	Cephaloglycin may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Flurbiprofen	Flurbiprofen may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Adefovir dipivoxil	Adefovir dipivoxil may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Pentamidine	Pentamidine may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Etodolac	Etodolac may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Acyclovir	Acyclovir may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Naproxen	Naproxen may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Sulfasalazine	Sulfasalazine may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Phenylbutazone	Phenylbutazone may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Meloxicam	Meloxicam may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Carprofen	Carprofen may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Cefaclor	Cefaclor may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Diflunisal	Diflunisal may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Tacrolimus	Tacrolimus may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Ceforanide	Ceforanide may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Salicylic acid	Salicylic acid may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Meclofenamic acid	Meclofenamic acid may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Acetylsalicylic acid	Acetylsalicylic acid may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Carboplatin	Carboplatin may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Oxaprozin	Oxaprozin may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Ketoprofen	Ketoprofen may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Balsalazide	Balsalazide may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Ibuprofen	Ibuprofen may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Cefditoren	Cefditoren may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Atazanavir	Atazanavir may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Colistimethate	Colistimethate may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Cefuroxime	Cefuroxime may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Cefapirin	Cefapirin may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Cefadroxil	Cefadroxil may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Cefprozil	Cefprozil may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Ceftriaxone	Ceftriaxone may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Olsalazine	Olsalazine may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Lumiracoxib	Lumiracoxib may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Cefamandole	Cefamandole may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Cefazolin	Cefazolin may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Cefonicid	Cefonicid may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Cefoperazone	Cefoperazone may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Cefotetan	Cefotetan may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Cefoxitin	Cefoxitin may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Ceftizoxime	Ceftizoxime may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Cefradine	Cefradine may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Magnesium salicylate	Magnesium salicylate may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Salsalate	Salsalate may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Choline magnesium trisalicylate	Choline magnesium trisalicylate may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Cefepime	Cefepime may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Cefacetrile	Cefacetrile may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Ceftibuten	Ceftibuten may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Cefpodoxime	Cefpodoxime may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Antrafenine	Antrafenine may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Aminophenazone	Aminophenazone may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Antipyrine	Antipyrine may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Tiaprofenic acid	Tiaprofenic acid may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Lopinavir	Lopinavir may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Etoricoxib	Etoricoxib may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Hydrolyzed Cephalothin	Hydrolyzed Cephalothin may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Cephalothin Group	Cephalothin Group may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Oxyphenbutazone	Oxyphenbutazone may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Latamoxef	Latamoxef may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Nimesulide	Nimesulide may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Benoxaprofen	Benoxaprofen may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Metamizole	Metamizole may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Zomepirac	Zomepirac may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Ceftobiprole	Ceftobiprole may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Cimicoxib	Cimicoxib may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Ceftaroline fosamil	Ceftaroline fosamil may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Lornoxicam	Lornoxicam may decrease the excretion rate of Nalmefene which could result in a higher serum level.
Aceclofenac	Aceclofenac may decrease the excretion rate of Nalmefene which could result in a higher serum level.

Target Protein

Kappa-type opioid receptor OPRK1

Delta-type opioid receptor OPRD1

Mu-type opioid receptor OPRM1

Referensi & Sumber

Artikel (PubMed)

PMID: 25187751
Paille F, Martini H: Nalmefene: a new approach to the treatment of alcohol dependence. Subst Abuse Rehabil. 2014 Aug 8;5:87-94. doi: 10.2147/SAR.S45666. eCollection 2014.
PMID: 8109774
Glass PS, Jhaveri RM, Smith LR: Comparison of potency and duration of action of nalmefene and naloxone. Anesth Analg. 1994 Mar;78(3):536-41.
PMID: 27842940
Mann K, Torup L, Sorensen P, Gual A, Swift R, Walker B, van den Brink W: Nalmefene for the management of alcohol dependence: review on its pharmacology, mechanism of action and meta-analysis on its clinical efficacy. Eur Neuropsychopharmacol. 2016 Dec;26(12):1941-1949. doi: 10.1016/j.euroneuro.2016.10.008. Epub 2016 Nov 12.
PMID: 31643618
Authors unspecified: Nalmefene .
PMID: 19789384
Le Merrer J, Becker JA, Befort K, Kieffer BL: Reward processing by the opioid system in the brain. Physiol Rev. 2009 Oct;89(4):1379-412. doi: 10.1152/physrev.00005.2009.
PMID: 22020140
Al-Hasani R, Bruchas MR: Molecular mechanisms of opioid receptor-dependent signaling and behavior. Anesthesiology. 2011 Dec;115(6):1363-81. doi: 10.1097/ALN.0b013e318238bba6.

Link

Contoh Produk & Brand

Produk: 14 • International brands: 0

Produk

Nalmefene Hydrochloride

Injection, solution • 1 mg/1mL • Intramuscular; Intravenous; Subcutaneous • US • Generic • Approved
Nalmefene Hydrochloride

Solution • 0.1 mg/1mL • Intramuscular; Intravenous; Subcutaneous • US • Generic • Approved
Nalmefene Hydrochloride

Solution • 2 mg/2mL • Intramuscular; Intravenous; Subcutaneous • US • Generic • Approved
Opvee

Spray • 2.7 mg/100uL • Nasal • US • Approved
Revex

Injection, solution • 0.1 mg/1mL • Intravenous • US • Approved
Revex

Injection, solution • 1 mg/1mL • Intravenous • US • Approved
Selincro

Tablet, film coated • 18 mg • Oral • EU • Approved
Selincro

Tablet, film coated • 18 mg • Oral • EU • Approved

Menampilkan 8 dari 14 produk.

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.