Peringatan Keamanan

Lofexidine did not exhibit genotoxic, mutagenic nor mutagenic potential. Administration at gestational period showed a reduction in the neonatal weight, survival, and increased abortion.L2801

Lofexidine

DB04948

small molecule approved investigational

Deskripsi

Lofexidine is a non-opioid centrally acting alpha2-adrenergic receptor agonist that was first approved for the treatment of opioid withdrawal in the United Kingdom in 1992.A33084 It was first studied for use as an antihypertensive in 1980, but its researched was stopped as it was found less effective for the treatment of hypertension than clonidine.T210 Lofexidine was then repurposed for the treatment of opioid withdrawal, as it was seen to be more economical and have fewer side effects than clonidine.T209 Lofexidine was developed by US Woldmeds LLC and it was approved by the FDA on May 16, 2018.L2794

Struktur Molekul 2D

Berat 259.132
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) The reported elimination half-life of lofexidine is 11 hours.[T55]
Volume Distribusi Lofexidine has a volume of distribution of 300 L, indicating that it distributes readily into the tissues.[L2801]
Klirens (Clearance) The total elimination clearance following intravenous administration is 17.6 L/h.[L2801]

Absorpsi

Lofexidine has a good oral bioavailability and the peak plasma concentration occurs after 2-5 hours of oral administration.T210 The bioavailability is registered to be even higher than 72%.T55 About 30% of the administered dose of lofexidine is lost during first-pass metabolism. The absorption is registered to be very rapidly recirculated in the gut. After oral administration of 0.8 mg of lofexidine, a maximal dose of 1.26 ng/ml is achieved after 3 hours.L2801

Metabolisme

Lofexidine metabolic ratio is highly variable among people.T210 It is metabolized mainly by the activity of CYP2D6 and in a minor degree by CYP1A2 and CYP2C19. These enzymes catalyze the hydroxylation of lofexidine and the opening of imidazoline ring to form N-(2-aminoethyl)-2-(2,6-dichlorophenoxy)propanamide. This metabolite is deamidated and forms 2-(2,6-dichlorophenoxy) propionic acid and 2,6-dichlorophenol. These three main metabolites are inactive.L2801

Rute Eliminasi

The elimination of lofexidine is primarily through the renal system and it represents 94% of the administered dose while elimination in feces corresponds to only 0.93%.T210 From the eliminated dose in urine, about 10% is formed by unchanged drug and 5% is constituted by the first hydrolysis product N-(2-aminoethyl)-2-(2,6-dichlorophenoxy)propanamide. 2,6-dichlorophenol represents the majority of the administered dose by occupying about 80% of the administered dose.L2801

Interaksi Makanan

2 Data
  • 1. Avoid excessive or chronic alcohol consumption. Lofexidine may potentiate the CNS depressant effects of alcohol.
  • 2. Take with or without food.

Interaksi Obat

2030 Data
Ivabradine Ivabradine may increase the QTc-prolonging activities of Lofexidine.
Deferasirox The serum concentration of Lofexidine can be increased when it is combined with Deferasirox.
Peginterferon alfa-2b The serum concentration of Lofexidine can be increased when it is combined with Peginterferon alfa-2b.
Leflunomide The serum concentration of Lofexidine can be decreased when it is combined with Leflunomide.
Teriflunomide The serum concentration of Lofexidine can be decreased when it is combined with Teriflunomide.
Alfuzosin Alfuzosin may increase the hypotensive activities of Lofexidine.
Amifostine Lofexidine may increase the hypotensive activities of Amifostine.
Diazoxide Diazoxide may increase the hypotensive activities of Lofexidine.
Methylphenidate Methylphenidate may decrease the antihypertensive activities of Lofexidine.
Obinutuzumab Lofexidine may increase the hypotensive activities of Obinutuzumab.
Pentoxifylline Pentoxifylline may increase the hypotensive activities of Lofexidine.
Rituximab Lofexidine may increase the hypotensive activities of Rituximab.
Epicaptopril Epicaptopril may decrease the antihypertensive activities of Lofexidine.
Siponimod Siponimod may decrease the antihypertensive activities of Lofexidine.
Valsartan Lofexidine may decrease the antihypertensive activities of Valsartan.
Ramipril Lofexidine may decrease the antihypertensive activities of Ramipril.
Olmesartan Lofexidine may decrease the antihypertensive activities of Olmesartan.
Minoxidil Lofexidine may decrease the antihypertensive activities of Minoxidil.
Trandolapril Lofexidine may decrease the antihypertensive activities of Trandolapril.
Benazepril Lofexidine may decrease the antihypertensive activities of Benazepril.
Enalapril Lofexidine may decrease the antihypertensive activities of Enalapril.
Nitroglycerin Lofexidine may decrease the antihypertensive activities of Nitroglycerin.
Candesartan cilexetil Lofexidine may decrease the antihypertensive activities of Candesartan cilexetil.
Eprosartan Lofexidine may decrease the antihypertensive activities of Eprosartan.
Quinapril Lofexidine may decrease the antihypertensive activities of Quinapril.
Telmisartan Lofexidine may decrease the antihypertensive activities of Telmisartan.
Irbesartan Lofexidine may decrease the antihypertensive activities of Irbesartan.
Captopril Lofexidine may decrease the antihypertensive activities of Captopril.
Cilazapril Lofexidine may decrease the antihypertensive activities of Cilazapril.
Remikiren Lofexidine may decrease the antihypertensive activities of Remikiren.
Bethanidine Bethanidine may decrease the antihypertensive activities of Lofexidine.
Guanadrel Lofexidine may decrease the antihypertensive activities of Guanadrel.
Bosentan Lofexidine may decrease the antihypertensive activities of Bosentan.
Candoxatril Lofexidine may decrease the antihypertensive activities of Candoxatril.
Cryptenamine Lofexidine may decrease the antihypertensive activities of Cryptenamine.
Omapatrilat Omapatrilat may decrease the antihypertensive activities of Lofexidine.
Deserpidine Lofexidine may decrease the antihypertensive activities of Deserpidine.
Pentolinium Lofexidine may decrease the antihypertensive activities of Pentolinium.
Trimethaphan Lofexidine may decrease the antihypertensive activities of Trimethaphan.
Rescinnamine Rescinnamine may decrease the antihypertensive activities of Lofexidine.
Saprisartan Lofexidine may decrease the antihypertensive activities of Saprisartan.
Spirapril Lofexidine may decrease the antihypertensive activities of Spirapril.
Debrisoquine Lofexidine may decrease the antihypertensive activities of Debrisoquine.
Sitaxentan Lofexidine may decrease the antihypertensive activities of Sitaxentan.
Ambrisentan Lofexidine may decrease the antihypertensive activities of Ambrisentan.
Diethylnorspermine Lofexidine may decrease the antihypertensive activities of Diethylnorspermine.
Pinacidil Lofexidine may decrease the antihypertensive activities of Pinacidil.
Temocapril Lofexidine may decrease the antihypertensive activities of Temocapril.
Riociguat Lofexidine may decrease the antihypertensive activities of Riociguat.
Aliskiren Lofexidine may decrease the antihypertensive activities of Aliskiren.
Moxonidine Lofexidine may decrease the antihypertensive activities of Moxonidine.
Rauwolfia serpentina root Lofexidine may decrease the antihypertensive activities of Rauwolfia serpentina root.
Selexipag Lofexidine may decrease the antihypertensive activities of Selexipag.
Angiotensin 1-7 Lofexidine may decrease the antihypertensive activities of Angiotensin 1-7.
Rilmenidine Lofexidine may decrease the antihypertensive activities of Rilmenidine.
Imidapril Lofexidine may decrease the antihypertensive activities of Imidapril.
BQ-123 Lofexidine may decrease the antihypertensive activities of BQ-123.
Naftopidil Lofexidine may decrease the antihypertensive activities of Naftopidil.
Zofenopril Lofexidine may decrease the antihypertensive activities of Zofenopril.
Guanoxan Lofexidine may decrease the antihypertensive activities of Guanoxan.
Delapril Lofexidine may decrease the antihypertensive activities of Delapril.
Vincamine Lofexidine may decrease the antihypertensive activities of Vincamine.
Linsidomine Lofexidine may decrease the antihypertensive activities of Linsidomine.
Guanoxabenz Lofexidine may decrease the antihypertensive activities of Guanoxabenz.
Tolonidine Lofexidine may decrease the antihypertensive activities of Tolonidine.
Endralazine Lofexidine may decrease the antihypertensive activities of Endralazine.
Cadralazine Lofexidine may decrease the antihypertensive activities of Cadralazine.
Bietaserpine Lofexidine may decrease the antihypertensive activities of Bietaserpine.
Guanazodine Lofexidine may decrease the antihypertensive activities of Guanazodine.
Methoserpidine Lofexidine may decrease the antihypertensive activities of Methoserpidine.
Guanoclor Lofexidine may decrease the antihypertensive activities of Guanoclor.
Candesartan Lofexidine may decrease the antihypertensive activities of Candesartan.
Dexniguldipine Lofexidine may decrease the antihypertensive activities of Dexniguldipine.
Tocopherylquinone Lofexidine may decrease the antihypertensive activities of Tocopherylquinone.
Benazeprilat Lofexidine may decrease the antihypertensive activities of Benazeprilat.
Fosinoprilat Lofexidine may decrease the antihypertensive activities of Fosinoprilat.
Ramiprilat Lofexidine may decrease the antihypertensive activities of Ramiprilat.
Perindoprilat Lofexidine may decrease the antihypertensive activities of Perindoprilat.
Quinaprilat Lofexidine may decrease the antihypertensive activities of Quinaprilat.
Isoxsuprine Isoxsuprine may decrease the antihypertensive activities of Lofexidine.
Midodrine Midodrine may decrease the antihypertensive activities of Lofexidine.
Amlodipine Lofexidine may decrease the antihypertensive activities of Amlodipine.
Selpercatinib Selpercatinib may decrease the antihypertensive activities of Lofexidine.
Naxitamab Naxitamab may decrease the antihypertensive activities of Lofexidine.
Levamlodipine Lofexidine may decrease the antihypertensive activities of Levamlodipine.
Lercanidipine Lofexidine may decrease the antihypertensive activities of Lercanidipine.
Doxylamine Doxylamine may increase the central nervous system depressant (CNS depressant) activities of Lofexidine.
Metyrosine Lofexidine may increase the sedative activities of Metyrosine.
Minocycline Minocycline may increase the central nervous system depressant (CNS depressant) activities of Lofexidine.
Pramipexole Lofexidine may increase the sedative activities of Pramipexole.
Ropinirole Lofexidine may increase the sedative activities of Ropinirole.
Tapentadol Tapentadol may increase the central nervous system depressant (CNS depressant) activities of Lofexidine.
Thalidomide Lofexidine may increase the central nervous system depressant (CNS depressant) activities of Thalidomide.
Isoetharine Isoetharine may decrease the antihypertensive activities of Lofexidine.
Norepinephrine Norepinephrine may decrease the antihypertensive activities of Lofexidine.
Phenylpropanolamine Phenylpropanolamine may decrease the antihypertensive activities of Lofexidine.
Doxapram Doxapram may decrease the antihypertensive activities of Lofexidine.
Metaraminol Metaraminol may decrease the antihypertensive activities of Lofexidine.
Epinephrine Epinephrine may decrease the antihypertensive activities of Lofexidine.
Methoxamine Methoxamine may decrease the antihypertensive activities of Lofexidine.

Target Protein

Alpha-2A adrenergic receptor ADRA2A
Alpha-1A adrenergic receptor ADRA1A
5-hydroxytryptamine receptor 1A HTR1A
5-hydroxytryptamine receptor 7 HTR7
5-hydroxytryptamine receptor 2C HTR2C
5-hydroxytryptamine receptor 1D HTR1D

Referensi & Sumber

Synthesis reference: U.S. Patent 3,966,757.
Artikel (PubMed)
  • PMID: 12653813
    Walsh SL, Strain EC, Bigelow GE: Evaluation of the effects of lofexidine and clonidine on naloxone-precipitated withdrawal in opioid-dependent humans. Addiction. 2003 Apr;98(4):427-39.
  • PMID: 18161012
    Haney M, Hart CL, Vosburg SK, Comer SD, Reed SC, Foltin RW: Effects of THC and lofexidine in a human laboratory model of marijuana withdrawal and relapse. Psychopharmacology (Berl). 2008 Mar;197(1):157-68. doi: 10.1007/s00213-007-1020-8. Epub 2007 Dec 27.
  • PMID: 23244430
    Rehni AK, Jaggi AS, Singh N: Opioid withdrawal syndrome: emerging concepts and novel therapeutic targets. CNS Neurol Disord Drug Targets. 2013 Feb 1;12(1):112-25.
  • PMID: 23073725
    Juurlink DN, Dhalla IA: Dependence and addiction during chronic opioid therapy. J Med Toxicol. 2012 Dec;8(4):393-9. doi: 10.1007/s13181-012-0269-4.
Textbook
  • ISBN: 978-0-7817-7477-2
    Ries R. and Miller S. (2009). Principles of Addiction Medicine (4th ed.). Lippincott Williams & Wilkins.
  • ISBN: 0-8018-8303-2
    Strain E. and Stitzer M. (2006). The treatment of Opiod Dependence. The Johns Hopkins University Press.
  • Zaragoza Dorwald F. (2012). Lead optimization for medicinal chemists. Wiley-VCH.

Contoh Produk & Brand

Produk: 5 • International brands: 1
Produk
  • Lofexidine
    Tablet, coated • 0.18 mg/1 • Oral • US • Generic • Approved
  • Lofexidine
    Tablet, coated • 0.18 mg/1 • Oral • US • Generic • Approved
  • Lofexidine hydrochloride
    Tablet, film coated • 0.2 mg/1 • Oral • US • Generic • Approved
  • Lucemyra
    Tablet, film coated • 0.2 mg/1 • Oral • US • Approved
  • Lucemyra
    Tablet, film coated • 0.2 mg/1 • Oral • US • Approved
International Brands
  • Britlofex — Britannia

Sekuens Gen/Protein (FASTA)

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