Peringatan Keamanan

Overdosage with mitotane can occur when plasma levels are above 20 mg/L.^L49570 Symptoms can include central nervous system toxicity, including sedation, lethargy, and vertigo, as well as muscular weakness and gait disturbance.^L49570 Mitotane is lipophilic and may therefore take weeks to adequately clear from a patient. It is unlikely to be dialyzable. In the event of a suspected overdose, consider increasing the frequency of mitotane plasma level monitoring. Withhold mitotane as clinically indicated for signs or symptoms of toxicity.^L49570

Mitotane

DB00648

small molecule approved

Deskripsi

Mitotane is an adrenolytic isomer of the insecticide dichlorodiphenyldichloroethane (DDD) - itself a metabolite of dichlorodiphenyltrichloroethane (DDT) - that inhibits cells of the adrenal cortex and their production of hormones. It has been in use since 1959 for the treatment of inoperable adrenocortical carcinoma^A263010 and is used off-label for the management of Cushing's syndrome.^A263016

Struktur Molekul 2D

Berat 320.041

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 plasma terminal half-life of mitotane ranges from 18 to 159 days, with a median of 53 days.[L49570]

Volume Distribusi Mitotane is extensively distributed and found in most tissues in the body.[L49570] Fat is the primary site of distribution.[L49570]

Klirens (Clearance) -

Absorpsi

The bioavailability of mitotane following oral administration is 40%.^L49570

Metabolisme

Mitotane undergoes extensive metabolism - both hepatic and extrahepatic - and no unchanged parent drug is excreted in the bile or urine.^L49570 The major circulating metabolite of mitotane is 1,1-(o,p'-dichlorodiphenyl) acetic acid (o,p’-DDA).^L49570

Rute Eliminasi

Approximately 10% of an administered dose is recovered in the urine as water-soluble metabolites, with a varying amount of metabolite (1%-17%) excreted in the bile.^L49570

Interaksi Makanan

1 Data

1. Take with food. The timing of mitotane administration relative to food intake should remain consistent. Co-administration with high-fat food enhances absorption.

Interaksi Obat

857 Data

Aripiprazole	The metabolism of Aripiprazole can be increased when combined with Mitotane.
Spironolactone	The therapeutic efficacy of Mitotane can be decreased when used in combination with Spironolactone.
Flunisolide	The serum concentration of Flunisolide can be decreased when it is combined with Mitotane.
Beclomethasone dipropionate	The serum concentration of Beclomethasone dipropionate can be decreased when it is combined with Mitotane.
Betamethasone	The serum concentration of Betamethasone can be decreased when it is combined with Mitotane.
Fluticasone propionate	The serum concentration of Fluticasone propionate can be decreased when it is combined with Mitotane.
Fluocinolone acetonide	The serum concentration of Fluocinolone acetonide can be decreased when it is combined with Mitotane.
Triamcinolone	The serum concentration of Triamcinolone can be decreased when it is combined with Mitotane.
Prednisone	The serum concentration of Prednisone can be decreased when it is combined with Mitotane.
Fludrocortisone	The serum concentration of Fludrocortisone can be decreased when it is combined with Mitotane.
Hydrocortisone	The serum concentration of Hydrocortisone can be decreased when it is combined with Mitotane.
Prednisolone	The serum concentration of Prednisolone can be decreased when it is combined with Mitotane.
Methylprednisolone	The serum concentration of Methylprednisolone can be decreased when it is combined with Mitotane.
Trilostane	The serum concentration of Trilostane can be decreased when it is combined with Mitotane.
Budesonide	The serum concentration of Budesonide can be decreased when it is combined with Mitotane.
Dexamethasone	The serum concentration of Dexamethasone can be decreased when it is combined with Mitotane.
Corticotropin	The serum concentration of Corticotropin can be decreased when it is combined with Mitotane.
Cortisone acetate	The serum concentration of Cortisone acetate can be decreased when it is combined with Mitotane.
Paramethasone	The serum concentration of Paramethasone can be decreased when it is combined with Mitotane.
Ciclesonide	The serum concentration of Ciclesonide can be decreased when it is combined with Mitotane.
Aldosterone	The serum concentration of Aldosterone can be decreased when it is combined with Mitotane.
Fluticasone furoate	The serum concentration of Fluticasone furoate can be decreased when it is combined with Mitotane.
Fluprednidene	The serum concentration of Fluprednidene can be decreased when it is combined with Mitotane.
Tixocortol	The serum concentration of Tixocortol can be decreased when it is combined with Mitotane.
Fluprednisolone	The serum concentration of Fluprednisolone can be decreased when it is combined with Mitotane.
Meprednisone	The serum concentration of Meprednisone can be decreased when it is combined with Mitotane.
Dexamethasone isonicotinate	The serum concentration of Dexamethasone isonicotinate can be decreased when it is combined with Mitotane.
Melengestrol	The serum concentration of Melengestrol can be decreased when it is combined with Mitotane.
Cortivazol	The serum concentration of Cortivazol can be decreased when it is combined with Mitotane.
Prednylidene	The serum concentration of Prednylidene can be decreased when it is combined with Mitotane.
Fluocortin	The serum concentration of Fluocortin can be decreased when it is combined with Mitotane.
Fluperolone	The serum concentration of Fluperolone can be decreased when it is combined with Mitotane.
Cloprednol	The serum concentration of Cloprednol can be decreased when it is combined with Mitotane.
Fluclorolone	The serum concentration of Fluclorolone can be decreased when it is combined with Mitotane.
Fluticasone	The serum concentration of Fluticasone can be decreased when it is combined with Mitotane.
Mometasone furoate	The serum concentration of Mometasone furoate can be decreased when it is combined with Mitotane.
Hydrocortisone acetate	The serum concentration of Hydrocortisone acetate can be decreased when it is combined with Mitotane.
Hydrocortisone cypionate	The serum concentration of Hydrocortisone cypionate can be decreased when it is combined with Mitotane.
Hydrocortisone succinate	The serum concentration of Hydrocortisone succinate can be decreased when it is combined with Mitotane.
Prednisolone phosphate	The serum concentration of Prednisolone phosphate can be decreased when it is combined with Mitotane.
Prednisolone hemisuccinate	The serum concentration of Prednisolone hemisuccinate can be decreased when it is combined with Mitotane.
Methylprednisolone hemisuccinate	The serum concentration of Methylprednisolone hemisuccinate can be decreased when it is combined with Mitotane.
Prednisone acetate	The serum concentration of Prednisone acetate can be decreased when it is combined with Mitotane.
Clocortolone acetate	The serum concentration of Clocortolone acetate can be decreased when it is combined with Mitotane.
Melengestrol acetate	The serum concentration of Melengestrol acetate can be decreased when it is combined with Mitotane.
Betamethasone phosphate	The serum concentration of Betamethasone phosphate can be decreased when it is combined with Mitotane.
Cortisone	The serum concentration of Cortisone can be decreased when it is combined with Mitotane.
Clobetasol propionate	The serum concentration of Clobetasol propionate can be decreased when it is combined with Mitotane.
Fluocinonide	The serum concentration of Fluocinonide can be decreased when it is combined with Mitotane.
Hydrocortisone butyrate	The serum concentration of Hydrocortisone butyrate can be decreased when it is combined with Mitotane.
Desoximetasone	The serum concentration of Desoximetasone can be decreased when it is combined with Mitotane.
Mometasone	The serum concentration of Mometasone can be decreased when it is combined with Mitotane.
Fluocortolone	The serum concentration of Fluocortolone can be decreased when it is combined with Mitotane.
Prednisolone acetate	The serum concentration of Prednisolone acetate can be decreased when it is combined with Mitotane.
Fluorometholone	The serum concentration of Fluorometholone can be decreased when it is combined with Mitotane.
Difluocortolone	The serum concentration of Difluocortolone can be decreased when it is combined with Mitotane.
Flumethasone	The serum concentration of Flumethasone can be decreased when it is combined with Mitotane.
Methylprednisolone aceponate	The serum concentration of Methylprednisolone aceponate can be decreased when it is combined with Mitotane.
Ifosfamide	The metabolism of Ifosfamide can be increased when combined with Mitotane.
Perampanel	The metabolism of Perampanel can be increased when combined with Mitotane.
Warfarin	The metabolism of Warfarin can be increased when combined with Mitotane.
Acenocoumarol	The metabolism of Acenocoumarol can be increased when combined with Mitotane.
(R)-warfarin	The metabolism of (R)-warfarin can be increased when combined with Mitotane.
R,S-Warfarin alcohol	The metabolism of R,S-Warfarin alcohol can be increased when combined with Mitotane.
S,R-Warfarin alcohol	The metabolism of S,R-Warfarin alcohol can be increased when combined with Mitotane.
(S)-Warfarin	The metabolism of (S)-Warfarin can be increased when combined with Mitotane.
Segesterone acetate	The metabolism of Segesterone acetate can be increased when combined with Mitotane.
Milnacipran	The metabolism of Milnacipran can be increased when combined with Mitotane.
Levomilnacipran	The metabolism of Levomilnacipran can be increased when combined with Mitotane.
Retapamulin	The metabolism of Retapamulin can be increased when combined with Mitotane.
Liothyronine	The therapeutic efficacy of Liothyronine can be decreased when used in combination with Mitotane.
Mephenytoin	The therapeutic efficacy of Mephenytoin can be decreased when used in combination with Mitotane.
Furosemide	The therapeutic efficacy of Furosemide can be decreased when used in combination with Mitotane.
Nitrofurantoin	The therapeutic efficacy of Nitrofurantoin can be decreased when used in combination with Mitotane.
Ethotoin	The therapeutic efficacy of Ethotoin can be decreased when used in combination with Mitotane.
Meclofenamic acid	The therapeutic efficacy of Meclofenamic acid can be decreased when used in combination with Mitotane.
Heparin	The therapeutic efficacy of Heparin can be decreased when used in combination with Mitotane.
Etofenamate	The therapeutic efficacy of Etofenamate can be decreased when used in combination with Mitotane.
Liothyronine I-131	The therapeutic efficacy of Liothyronine I-131 can be decreased when used in combination with Mitotane.
Neocitrullamon	The therapeutic efficacy of Neocitrullamon can be decreased when used in combination with Mitotane.
Dantrolene	The therapeutic efficacy of Dantrolene can be decreased when used in combination with Mitotane.
Levothyroxine	The therapeutic efficacy of Levothyroxine can be decreased when used in combination with Mitotane.
Allantoin	The therapeutic efficacy of Allantoin can be decreased when used in combination with Mitotane.
Clonazepam	The metabolism of Clonazepam can be increased when combined with Mitotane.
Tezacaftor	The serum concentration of Tezacaftor can be decreased when it is combined with Mitotane.
Eszopiclone	The serum concentration of Eszopiclone can be decreased when it is combined with Mitotane.
Lefamulin	The metabolism of Lefamulin can be increased when combined with Mitotane.
Elexacaftor	The serum concentration of Elexacaftor can be decreased when it is combined with Mitotane.
Lemborexant	The serum concentration of Lemborexant can be decreased when it is combined with Mitotane.
Lumateperone	The serum concentration of Lumateperone can be decreased when it is combined with Mitotane.
Ranolazine	The metabolism of Ranolazine can be increased when combined with Mitotane.
Tramadol	The metabolism of Tramadol can be increased when combined with Mitotane.
Clindamycin	The metabolism of Clindamycin can be increased when combined with Mitotane.
Rimegepant	The metabolism of Rimegepant can be increased when combined with Mitotane.
Tucatinib	The metabolism of Tucatinib can be increased when combined with Mitotane.
Capmatinib	The serum concentration of Capmatinib can be decreased when it is combined with Mitotane.
Selpercatinib	The serum concentration of Selpercatinib can be decreased when it is combined with Mitotane.
Fostemsavir	The serum concentration of Fostemsavir can be decreased when it is combined with Mitotane.
Oliceridine	The serum concentration of Oliceridine can be decreased when it is combined with Mitotane.
Relugolix	The serum concentration of Relugolix can be decreased when it is combined with Mitotane.

Target Protein

Cytochrome P450 11B1, mitochondrial CYP11B1

Estrogen receptor ESR1

Progesterone receptor PGR

Androgen receptor AR

Adrenodoxin, mitochondrial FDX1

Referensi & Sumber

Artikel (PubMed)

PMID: 28456766
Waszut U, Szyszka P, Dworakowska D: Understanding mitotane mode of action. J Physiol Pharmacol. 2017 Feb;68(1):13-26.
PMID: 29855779
Broersen LHA, Jha M, Biermasz NR, Pereira AM, Dekkers OM: Effectiveness of medical treatment for Cushing's syndrome: a systematic review and meta-analysis. Pituitary. 2018 Dec;21(6):631-641. doi: 10.1007/s11102-018-0897-z.

Link

Contoh Produk & Brand

Produk: 4 • International brands: 2

Produk

Lysodren

Tablet • 500 mg/1 • Oral • US • Approved
Lysodren

Tablet • 500 mg/1 • Oral • US • Approved
Lysodren

Tablet • 500 mg • Oral • Canada • Approved
Lysodren

Tablet • 500 mg • Oral • EU • Approved

International Brands

Lisodren — Bristol-Myers Squibb
Opeprim — Yakult Honsha

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.