Peringatan Keamanan

Data regarding overdoses of trimetazidine are not readily available.L33015 Treat overdoses with symptomatic and supportive therapy.L33015

The oral LD50 in rats is 1700 mg/kg, and in mice is 1550 mg/kg.L33025 The subcutaneous LD50 in rats is 1500 mg/kg, and in mice is 410 mg/kg.L33025

Trimetazidine

DB09069

small molecule approved investigational

Deskripsi

Trimetazidine is a piperazine derivative indicated for the symptomatic treatment of stable angina pectoris in patients inadequately controlled or intolerant to first line therapies.L33015 Trimetazidine has been studied as a treatment for angina pectoris since the late 1960s.A233255,A233260

Acidic conditions, caused by anaerobic metabolism and fatty acid oxidation, in response to myocardial ischemia, activate sodium-hydrogen and sodium-calcium antiport systems.A233215 The increased intracellular calcium decreases contractility.A233215 It is hypothesized that trimetazidine inhibits 3-ketoacyl coenzyme A thiolase, which decreases fatty acid oxidation but not glucose metabolism, preventing the acidic conditions that exacerbate ischemic injury.A7688,L33020 However, evidence for this mechanism is controversial.A233215

Trimetazidine is not FDA approved. However, it has been approved in France since 1978.L33020

Struktur Molekul 2D

Berat 266.341
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) In young, healthy subjects, the half life of trimetazidine is 7.81 hours.[A7692,L33015] In patients over 65, the half life increases to 11.7 hours.[A7692,L33015]
Volume Distribusi The volume of distribution of trimetazidine is 4.8 L/kg.[L33015]
Klirens (Clearance) Trimetazidine clearance is strongly correlated with creatinine clearance.[L33015] In eldery patients with a creatinine clearance of 72 ± 8 mL/min, trimetazidine clearance was 15.69 L/h.[A7692] In young, healthy patients with a creatinine clearance of 134 ± 18 mL/min, trimetazidine clearance was 25.2 L/h.[A7692]

Absorpsi

In elderly patients, a 35 mg oral modified release tablet reaches a mean Cmax of 115 µg/L, with a Tmax of 2.0-5.0 hours, and a mean AUC0-12 of 1104 h\*µg/L.A7692 In young, healthy patients, the same dose reaches a mean Cmax of 91.2 µg/L, with a Tmax of 2.0-6.0 hours, and an AUC0-12h 720 h\*µg/L.A7692

Metabolisme

Trimetazidine can be oxidized at the piperazine ring to form trimetazidine ketopiperazine.A233230 Trimetazidine can also be N-formylated, N-acetylated, or N-methylated at the piperazine ring to form N-formyltrimetazidine, N-acetyltrimetazidine, and N-methyltrimetazidine respectively.A233230 Alternatively, trimetazidine can be demethylated at the 2, 3, or 4 position of the 2,3,4-trimethoxybenzyl moiety to form 2-desmethyltrimetazidine, 3-desmethyltrimetazidine, or 4-desmethyltrimetazidine.A233230 The desmethyltrimetazidine metabolites can undergo sulfate conjugation or glucuronidation prior to elimination.A233230

Rute Eliminasi

Trimetazidine is 79-84% eliminated in the urine, with 60% as the unchanged parent compound.A7692,L33015 In a study of 4 healthy subjects, individual metabolites made up 0.01-1.4% of the dose recovered in urine.A233230 In the urine, 2-desmethyltrimetazidine made up 0-1.4% of the recovered dose, 3- and 4-desmethyltrimetazidine made up 0.039-0.071% each, N-methyltrimetazidine made up 0.015-0.11%, trimetazidine ketopiperazine made up 0.011-0.4%, N-formyltrimetazidine made up 0.035-0.42%, N-acetyltrimetazidine made up 0.016-0.19%, desmethyl trimetazidine O-sulphate made up 0.01-0.65%, and an unknown metabolite made up0.026-0.67%.A233230

Interaksi Makanan

2 Data
  • 1. Take with food. Take during a meal.
  • 2. Take with plain water. Take with a glass of water.

Interaksi Obat

1 Data
Metoclopramide The risk or severity of adverse effects can be increased when Metoclopramide is combined with Trimetazidine.

Target Protein

3-ketoacyl-CoA thiolase, mitochondrial ACAA2

Referensi & Sumber

Artikel (PubMed)
  • PMID: 10720420
    Kantor PF, Lucien A, Kozak R, Lopaschuk GD: The antianginal drug trimetazidine shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-ketoacyl coenzyme A thiolase. Circ Res. 2000 Mar 17;86(5):580-8.
  • PMID: 10350001
    Reymond F, Steyaert G, Carrupt PA, Morin D, Tillement JP, Girault HH, Testa B: The pH-partition profile of the anti-ischemic drug trimetazidine may explain its reduction of intracellular acidosis. Pharm Res. 1999 May;16(5):616-24.
  • PMID: 12698499
    Barre J, Ledudal P, Oosterhuis B, Brakenhoff JP, Wilkens G, Sollie FA, Tran D: Pharmacokinetic profile of a modified release formulation of trimetazidine (TMZ MR 35 mg) in the elderly and patients with renal failure. Biopharm Drug Dispos. 2003 May;24(4):159-64.
  • PMID: 25440662
    Sun S, Long C, Tao C, Meng S, Deng B: Ultrasonic microdialysis coupled with capillary electrophoresis electrochemiluminescence study the interaction between trimetazidine dihydrochloride and human serum albumin. Anal Chim Acta. 2014 Dec 3;851:37-42. doi: 10.1016/j.aca.2014.08.012. Epub 2014 Aug 13.
  • PMID: 12869391
    MacInnes A, Fairman DA, Binding P, Rhodes Ja, Wyatt MJ, Phelan A, Haddock PS, Karran EH: The antianginal agent trimetazidine does not exert its functional benefit via inhibition of mitochondrial long-chain 3-ketoacyl coenzyme A thiolase. Circ Res. 2003 Aug 8;93(3):e26-32. doi: 10.1161/01.RES.0000086943.72932.71. Epub 2003 Jul 17.
  • PMID: 8868005
    Jackson PJ, Brownsill RD, Taylor AR, Resplandy G, Walther B, Schwietert HR: Identification of trimetazidine metabolites in human urine and plasma. Xenobiotica. 1996 Feb;26(2):221-8. doi: 10.3109/00498259609046702.
  • PMID: 4864732
    Mehrotra TN, Bassadone ET: Trimetazidine in the treatment of angina pectoris. Br J Clin Pract. 1967 Nov 11;21(11):553-4.
  • PMID: 4970482
    Brodbin P, O'Connor CA: Trimetazidine in the treatment of angina pectoris. Br J Clin Pract. 1968 Sep;22(9):395-6.

Contoh Produk & Brand

Produk: 0 • International brands: 1
International Brands
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