Pharmacology: Pharmacodynamics: In patients with ischemic heart disease, trimetazidine acts as a metabolic agent, preserving the myocardial high-energy phosphate intracellular levels. Anti-ischemic effects are achieved without concomitant hemodynamic effects.
Pharmacokinetics: Absorption: After oral administration, absorption of trimetazidine is rapid and the plasma peak is reached in less than 2 hours. After a single oral dose of 20 mg of trimetazidine, the peak plasma concentration is approximately 55 ng.ml-1. During repeated administration, the steady state is reached after 24 to 36 hours and remains very stable throughout treatment.
Distribution: The apparent distribution volume is 4.8 l/kg, which suggests good tissue diffusion. Protein binding is low: in vitro measurements give a value of 16%.
Elimination: Trimetazidine is eliminated primarily in the urine, mainly in the unchanged form. The mean elimination half-life is 6 hours.
Linearity: Trimetazidine pharmacokinetics is linear following single dose administration up to 100 mg. Repeated doses showed a time-linear pharmacokinetic response.
Elderly: Trimetazidine exposure may be increased in elderly patients due to an age-related decrease in renal function. A pharmacokinetics study performed specifically in elderly (75-84 years) and very elderly (≥85 years) participants showed that in the event of moderate renal impairment (creatinine clearance between 30 and 60 ml/min) trimetazidine exposure was increased by a factor of 1.0 and 1.3, respectively in comparison with younger participants (30-65 years) with moderate renal impairment. No safety concerns were observed in the elderly subjects as compared with the general population.
Renal impairment: On average, trimetazidine exposure is multiplied by 1.7 in patients with moderate renal impairment (creatinine clearance between 30 and 60 ml/min) and by 3.1 in patients with severe renal impairment (creatinine clearance below 30 ml/min) compared with healthy young volunteers with normal renal function. No safety concerns were observed in this population as compared with the general population.
Pediatric population: The pharmacokinetics of trimetazidine have not been studied in the pediatric population (<18 years).