Peringatan Keamanan

Oral LD50 values of doxepin in mouse and rat are 180 mg/kg and 147 mg/kg, respectively.MSDS In an overdose state, symptoms of convulsions, dysrhythmias, coma, severe hypotension, central nervous system depression, changes on electrocardiography results and death have been observed.T249

On fertility studies, doxepin was shown to increase the copulatory interval, decrease the corpora lutea, decrease implantation, decreased the number of viable embryos, decrease litter size, increase the number of abnormal sperm and decrease the sperm motility. There is no evidence indicating carcinogenic and mutagenic potential.^{FDA label}

Doxepin

DB01142

small molecule approved investigational

Deskripsi

Doxepin is a psychotropic agent with antidepressant and anxiolytic properties.T559 It is a tertiary amine that can be presented as (E) and (Z) stereoisomers with the (Z) stereoisomer corresponding to cidoxepin. Doxepin commonly produces a 5:1 (E):(Z) racemic mixture.T83

In a strict sense, doxepin is not a tricyclic antidepressant but it is commonly associated with the class since it shares a lot of properties with members of the drug family including amitriptyline, clomipramine, desipramine, imipramine, nortriptyline, protriptyline and trimipramine.^L5977

Doxepin was developed by Pfizer and FDA approved in 1969 as an antidepressant.^L5971 However, in 2010 it was approved for the treatment of insomnia. The latter indication was presented by Pernix Therapeutics.^L5974

Struktur Molekul 2D

Berat 279.3761

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 mean elimination half-life is reported to be of 15 hours.[T388]

Volume Distribusi The mean apparent volume of distribution of doxepin is reported to be of 20 L/kg.[T388]

Klirens (Clearance) The mean total apparent plasma clearance of a single oral dose of 50 mg doxepin in healthy individuals is 0.93 l/hr/kg.[A1945]

Absorpsi

Doxepin is moderately absorbed following oral ingestion with a bioavailability of 30%.T388 The median peak concentration of doxepin ranges from 8.8-45.8 ng/ml and it is achieved 3.5 hours after initial administration. Its absorption is increased with concomitant administration of a high-fat meal.^L5995

Metabolisme

Doxepin is extensively metabolized to N-desmethyldoxepin which is a biologically active metabolite and other inactive metabolites.^A177172 The first-pass metabolism accounts for 55-87% of the administered dose.^A177196 After, the secondary metabolism is driven by the transformation of N-desmethyldoxepin to its glucuronide conjugates.^L5995 The main metabolic enzymes involved in the transformation of doxepin are the members of the cytochrome P450 family, CYP2C19 and CYP2D6 with minor involvement of CYP1A2 and CYP2C9.^L5995

Rute Eliminasi

The elimination profile of doxepin is presented as biphasic.^A1945 It is excreted in the urine mainly in the form of glucuronide conjugates. Less than 3% of a doxepin dose is excreted in the urine as parent compound or nordoxepin.^L1347