Peringatan Keamanan

There is limited information regarding samidorphan overdose. During clinical trials for the combination of olanzapine and samidorphan, overdose was recognized in 7/861 patients, none of which were fatal. One patient who ingested 5.5- and 11-times the maximum daily dosage of olanzapine and samidorphan, respectively, was unresponsive and admitted to the hospital but stabilized within two days. As there are no known antidotes for overdose with this combination, symptomatic and supportive measures are recommended.L34359

Samidorphan

DB12543

small molecule approved investigational

Deskripsi

Olanzapine is an effective atypical antipsychotic that, like other antipsychotics, is associated with weight gain, metabolic dysfunction, and increased risk of type II diabetes.A235638, A235643 Samidorphan is a novel opioid antagonist structurally related to naltrexone, with a higher affinity for opioid receptors, more potent ?-opioid receptor antagonism, higher oral bioavailability, and a longer half-life, making it an attractive candidate for oral dosing.A235623, A235638, L34359 Although antipsychotic-induced weight gain is incompletely understood, it is thought that the opioid system plays a key role in feeding and metabolism, such that opioid antagonism may be expected to ameliorate these negative effects. Samidorphan has been shown in animal models and clinical trials to ameliorate olanzapine-induced weight gain and metabolic dysfunction.A235638, A235643

Samidorphan was first approved as a variety of fixed-dose combination tablets with olanzapine by the FDA on May 28, 2021, and is currently marketed under the trademark LYBALVI™ by Alkermes Inc.L34359

Struktur Molekul 2D

Berat 370.449
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) Samidorphan has a mean half-life of 7-11 hours.[A235653, A235658, A235663, L34359]
Volume Distribusi Samidorphan following a single 10 mg oral dose had an apparent volume of distribution between 336.59 ± 75.42 and 557.6 ± 120.51 L, depending on age, gender, and concomitant food consumption.[A235658]
Klirens (Clearance) Samidorphan has a mean clearance of 35-45 L/h.[A235658, L34359]

Absorpsi

Samidorphan pharmacokinetics are linear over the range of clinically relevant concentrations, and steady-state kinetics are reached by seven days with once-daily oral administration. Upon reaching steady-state, with a once-daily dose of 10 mg samidorphan combined with 20 mg olanzapine, samidorphan has a mean Cmax of 45.1 ± 11.4 ng/mL and an AUC24h of 364 ± 112 ng\*h/mL. Samidorphan has an absolute oral bioavailability of 69% and a Tmax of 1-2 hours.A235653, A235658, L34359 Samidorphan pharmacokinetics are not significantly impacted by food; following a high-fat meal, the Cmax was 0.85 (90% CI 0.76, 0.94) and the AUC 1.03 (90% CI 1.0, 1.05) that for the fasted state.A235658, A235663, L34359

Metabolisme

Samidorphan is primarily metabolized by CYP3A4, with minor contributions from CYP3A5, CYP2C19, and CYP2C8.L34359 The main metabolism products are RDC-9986 (an N-dealkylated metabolite) and RDC-1066 (an N-oxide metabolite); although both metabolites have a nanomolar affinity for the ?-, ?-, and ?-opioid receptors, neither is thought to contribute to the pharmacological effects of samidorphan.L34359, L34378

Rute Eliminasi

Samidorphan is primarily renally excreted, with 67% of unchanged parent and metabolites eliminated in urine and another 16% in feces.L34359

Interaksi Makanan

1 Data
  • 1. Take with or without food. Food has only a minor effect on samidorphan pharmacokinetics.

Interaksi Obat

779 Data
Methylnaltrexone Samidorphan may increase the opioid antagonism activities of Methylnaltrexone.
Naloxegol Samidorphan may increase the opioid antagonism activities of Naloxegol.
Pitolisant The serum concentration of Samidorphan can be decreased when it is combined with Pitolisant.
Metreleptin The metabolism of Samidorphan can be increased when combined with Metreleptin.
Tramadol The therapeutic efficacy of Tramadol can be decreased when used in combination with Samidorphan.
Morphine The risk or severity of CNS depression can be increased when Morphine is combined with Samidorphan.
Codeine The risk or severity of CNS depression can be increased when Codeine is combined with Samidorphan.
Hydromorphone The risk or severity of CNS depression can be increased when Hydromorphone is combined with Samidorphan.
Methadone The risk or severity of adverse effects can be increased when Methadone is combined with Samidorphan.
Meperidine The risk or severity of adverse effects can be increased when Meperidine is combined with Samidorphan.
Oxycodone The therapeutic efficacy of Oxycodone can be decreased when used in combination with Samidorphan.
Butorphanol The risk or severity of CNS depression can be increased when Butorphanol is combined with Samidorphan.
Dextropropoxyphene The risk or severity of CNS depression can be increased when Dextropropoxyphene is combined with Samidorphan.
Pentazocine The risk or severity of CNS depression can be increased when Pentazocine is combined with Samidorphan.
Naltrexone The therapeutic efficacy of Naltrexone can be decreased when used in combination with Samidorphan.
Sufentanil The risk or severity of CNS depression can be increased when Sufentanil is combined with Samidorphan.
Alfentanil The risk or severity of CNS depression can be increased when Alfentanil is combined with Samidorphan.
Fentanyl The risk or severity of adverse effects can be increased when Fentanyl is combined with Samidorphan.
Nalbuphine The risk or severity of CNS depression can be increased when Nalbuphine is combined with Samidorphan.
Levorphanol The risk or severity of CNS depression can be increased when Levorphanol is combined with Samidorphan.
Remifentanil The risk or severity of CNS depression can be increased when Remifentanil is combined with Samidorphan.
Buprenorphine Samidorphan may increase the central nervous system depressant (CNS depressant) activities of Buprenorphine.
Hydrocodone Samidorphan may increase the central nervous system depressant (CNS depressant) activities of Hydrocodone.
Diphenoxylate The risk or severity of CNS depression can be increased when Diphenoxylate is combined with Samidorphan.
Oxymorphone The risk or severity of CNS depression can be increased when Oxymorphone is combined with Samidorphan.
Dezocine The risk or severity of CNS depression can be increased when Dezocine is combined with Samidorphan.
Levacetylmethadol The risk or severity of CNS depression can be increased when Levacetylmethadol is combined with Samidorphan.
Methadyl acetate The risk or severity of CNS depression can be increased when Methadyl acetate is combined with Samidorphan.
Dihydroetorphine The risk or severity of CNS depression can be increased when Dihydroetorphine is combined with Samidorphan.
Diamorphine The risk or severity of CNS depression can be increased when Diamorphine is combined with Samidorphan.
Bezitramide The therapeutic efficacy of Bezitramide can be decreased when used in combination with Samidorphan.
Ethylmorphine The risk or severity of CNS depression can be increased when Ethylmorphine is combined with Samidorphan.
Etorphine The risk or severity of CNS depression can be increased when Etorphine is combined with Samidorphan.
Dextromoramide The risk or severity of CNS depression can be increased when Dextromoramide is combined with Samidorphan.
Desomorphine The risk or severity of CNS depression can be increased when Desomorphine is combined with Samidorphan.
Carfentanil The risk or severity of CNS depression can be increased when Carfentanil is combined with Samidorphan.
Dihydrocodeine The risk or severity of CNS depression can be increased when Dihydrocodeine is combined with Samidorphan.
Alphacetylmethadol The risk or severity of CNS depression can be increased when Alphacetylmethadol is combined with Samidorphan.
Dihydromorphine The risk or severity of CNS depression can be increased when Dihydromorphine is combined with Samidorphan.
Tapentadol Tapentadol may increase the central nervous system depressant (CNS depressant) activities of Samidorphan.
Ketobemidone The risk or severity of CNS depression can be increased when Ketobemidone is combined with Samidorphan.
DPDPE The risk or severity of CNS depression can be increased when DPDPE is combined with Samidorphan.
Lofentanil The risk or severity of CNS depression can be increased when Lofentanil is combined with Samidorphan.
Eluxadoline The therapeutic efficacy of Eluxadoline can be decreased when used in combination with Samidorphan.
Opium The risk or severity of CNS depression can be increased when Opium is combined with Samidorphan.
Normethadone The risk or severity of CNS depression can be increased when Normethadone is combined with Samidorphan.
Piritramide The risk or severity of CNS depression can be increased when Piritramide is combined with Samidorphan.
Alphaprodine The risk or severity of CNS depression can be increased when Samidorphan is combined with Alphaprodine.
Nicomorphine The risk or severity of CNS depression can be increased when Samidorphan is combined with Nicomorphine.
Meptazinol The risk or severity of CNS depression can be increased when Samidorphan is combined with Meptazinol.
Phenoperidine The risk or severity of CNS depression can be increased when Samidorphan is combined with Phenoperidine.
Phenazocine The risk or severity of CNS depression can be increased when Samidorphan is combined with Phenazocine.
Tilidine The risk or severity of CNS depression can be increased when Samidorphan is combined with Tilidine.
Carfentanil, C-11 The risk or severity of CNS depression can be increased when Samidorphan is combined with Carfentanil, C-11.
Benzhydrocodone The therapeutic efficacy of Benzhydrocodone can be decreased when used in combination with Samidorphan.
Oliceridine The risk or severity of hypotension, sedation, death, somnolence, and respiratory depression can be increased when Samidorphan is combined with Oliceridine.
Cenobamate The serum concentration of Samidorphan can be decreased when it is combined with Cenobamate.
Ritonavir The serum concentration of Samidorphan can be increased when it is combined with Ritonavir.
Haloperidol The risk or severity of CNS depression can be increased when Haloperidol is combined with Samidorphan.
Tucatinib The metabolism of Tucatinib can be decreased when combined with Samidorphan.
Abametapir The serum concentration of Samidorphan can be increased when it is combined with Abametapir.
Satralizumab The serum concentration of Samidorphan can be decreased when it is combined with Satralizumab.
Sotorasib The serum concentration of Samidorphan can be decreased when it is combined with Sotorasib.
Cyclosporine The metabolism of Samidorphan can be decreased when combined with Cyclosporine.
Fluvoxamine The risk or severity of adverse effects can be increased when Samidorphan is combined with Fluvoxamine.
Fluconazole The metabolism of Samidorphan can be decreased when combined with Fluconazole.
Erythromycin The serum concentration of Samidorphan can be increased when it is combined with Erythromycin.
Ziprasidone The risk or severity of adverse effects can be increased when Samidorphan is combined with Ziprasidone.
Isradipine The metabolism of Samidorphan can be decreased when combined with Isradipine.
Diltiazem The metabolism of Samidorphan can be decreased when combined with Diltiazem.
Clozapine The metabolism of Samidorphan can be decreased when combined with Clozapine.
Ciprofloxacin The metabolism of Samidorphan can be decreased when combined with Ciprofloxacin.
Nicardipine The metabolism of Samidorphan can be decreased when combined with Nicardipine.
Verapamil The metabolism of Samidorphan can be decreased when combined with Verapamil.
Aprepitant The metabolism of Samidorphan can be decreased when combined with Aprepitant.
Isoniazid The metabolism of Samidorphan can be decreased when combined with Isoniazid.
Primaquine The metabolism of Samidorphan can be decreased when combined with Primaquine.
Miconazole The metabolism of Samidorphan can be decreased when combined with Miconazole.
Fusidic acid The metabolism of Samidorphan can be decreased when combined with Fusidic acid.
Zimelidine The risk or severity of adverse effects can be increased when Samidorphan is combined with Zimelidine.
Dronedarone The metabolism of Samidorphan can be decreased when combined with Dronedarone.
Milnacipran The risk or severity of adverse effects can be increased when Samidorphan is combined with Milnacipran.
Simeprevir The metabolism of Samidorphan can be decreased when combined with Simeprevir.
Isavuconazonium The metabolism of Samidorphan can be decreased when combined with Isavuconazonium.
Desvenlafaxine The risk or severity of adverse effects can be increased when Samidorphan is combined with Desvenlafaxine.
Nilvadipine The metabolism of Samidorphan can be decreased when combined with Nilvadipine.
Seproxetine The risk or severity of adverse effects can be increased when Samidorphan is combined with Seproxetine.
Linagliptin The metabolism of Samidorphan can be decreased when combined with Linagliptin.
Indalpine The risk or severity of adverse effects can be increased when Samidorphan is combined with Indalpine.
Netupitant The metabolism of Samidorphan can be decreased when combined with Netupitant.
Barnidipine The metabolism of Samidorphan can be decreased when combined with Barnidipine.
Benidipine The metabolism of Samidorphan can be decreased when combined with Benidipine.
Venetoclax The metabolism of Samidorphan can be decreased when combined with Venetoclax.
Isavuconazole The metabolism of Samidorphan can be decreased when combined with Isavuconazole.
Fosnetupitant The metabolism of Samidorphan can be decreased when combined with Fosnetupitant.
Berotralstat The metabolism of Samidorphan can be decreased when combined with Berotralstat.
Midostaurin The metabolism of Samidorphan can be decreased when combined with Midostaurin.
Voriconazole The metabolism of Samidorphan can be decreased when combined with Voriconazole.
Danazol The metabolism of Samidorphan can be decreased when combined with Danazol.
Nelfinavir The metabolism of Samidorphan can be decreased when combined with Nelfinavir.

Target Protein

Mu-type opioid receptor OPRM1
Kappa-type opioid receptor OPRK1
Delta-type opioid receptor OPRD1

Referensi & Sumber

Synthesis reference: Wentland MP, Lu Q, Lou R, Bu Y, Knapp BI, Bidlack JM: Synthesis and opioid receptor binding properties of a highly potent 4-hydroxy analogue of naltrexone. Bioorg Med Chem Lett. 2005 Apr 15;15(8):2107-10. doi: 10.1016/j.bmcl.2005.02.032.
Artikel (PubMed)
  • PMID: 31523568
    Chaudhary AMD, Khan MF, Dhillon SS, Naveed S: A Review of Samidorphan: A Novel Opioid Antagonist. Cureus. 2019 Jul 15;11(7):e5139. doi: 10.7759/cureus.5139.
  • PMID: 30108159
    Bidlack JM, Knapp BI, Deaver DR, Plotnikava M, Arnelle D, Wonsey AM, Fern Toh M, Pin SS, Namchuk MN: In Vitro Pharmacological Characterization of Buprenorphine, Samidorphan, and Combinations Being Developed as an Adjunctive Treatment of Major Depressive Disorder. J Pharmacol Exp Ther. 2018 Nov;367(2):267-281. doi: 10.1124/jpet.118.249839. Epub 2018 Aug 14.
  • PMID: 15808478
    Wentland MP, Lu Q, Lou R, Bu Y, Knapp BI, Bidlack JM: Synthesis and opioid receptor binding properties of a highly potent 4-hydroxy analogue of naltrexone. Bioorg Med Chem Lett. 2005 Apr 15;15(8):2107-10. doi: 10.1016/j.bmcl.2005.02.032.
  • PMID: 19282177
    Wentland MP, Lou R, Lu Q, Bu Y, Denhardt C, Jin J, Ganorkar R, VanAlstine MA, Guo C, Cohen DJ, Bidlack JM: Syntheses of novel high affinity ligands for opioid receptors. Bioorg Med Chem Lett. 2009 Apr 15;19(8):2289-94. doi: 10.1016/j.bmcl.2009.02.078. Epub 2009 Feb 25.
  • PMID: 31294646
    Cunningham JI, Eyerman DJ, Todtenkopf MS, Dean RL, Deaver DR, Sanchez C, Namchuk M: Samidorphan mitigates olanzapine-induced weight gain and metabolic dysfunction in rats and non-human primates. J Psychopharmacol. 2019 Oct;33(10):1303-1316. doi: 10.1177/0269881119856850. Epub 2019 Jul 11.
  • PMID: 30845818
    Martin WF, Correll CU, Weiden PJ, Jiang Y, Pathak S, DiPetrillo L, Silverman BL, Ehrich EW: Mitigation of Olanzapine-Induced Weight Gain With Samidorphan, an Opioid Antagonist: A Randomized Double-Blind Phase 2 Study in Patients With Schizophrenia. Am J Psychiatry. 2019 Jun 1;176(6):457-467. doi: 10.1176/appi.ajp.2018.18030280. Epub 2019 Mar 8.
  • PMID: 30476361
    Pathak S, Vince B, Kelsh D, Setnik B, Nangia N, DiPetrillo L, Puhl MD, Sun L, Stanford AD, Ehrich E: Abuse Potential of Samidorphan: A Phase I, Oxycodone-, Pentazocine-, Naltrexone-, and Placebo-Controlled Study. J Clin Pharmacol. 2019 Feb;59(2):218-228. doi: 10.1002/jcph.1343. Epub 2018 Nov 26.
  • PMID: 30348514
    Sun L, McDonnell D, von Moltke L: Pharmacokinetics and Short-term Safety of ALKS 3831, a Fixed-dose Combination of Olanzapine and Samidorphan, in Adult Subjects with Schizophrenia. Clin Ther. 2018 Nov;40(11):1845-1854.e2. doi: 10.1016/j.clinthera.2018.09.002. Epub 2018 Oct 20.
Menampilkan 8 dari 10 artikel.

Contoh Produk & Brand

Produk: 4 • International brands: 0
Produk
  • Lybalvi
    Tablet, film coated • - • Oral • US • Approved
  • Lybalvi
    Tablet, film coated • - • Oral • US • Approved
  • Lybalvi
    Tablet, film coated • - • Oral • US • Approved
  • Lybalvi
    Tablet, film coated • - • Oral • US • Approved

Sekuens Gen/Protein (FASTA)

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