Pharmacokinetic profile of a modified release formulation of trimetazidine (TMZ MR 35 mg) in the elderly and patients with renal failure

Objectives - To study the effect of age and renal function on the pharmacokinetic profile of a modified release tablet of trimetazidine (TMZ MR 35 mg) administered twice daily. Methods - Study 1: Twelve healthy elderly subjects (CLcraet 72 +/- 8 ml/min, 72 +/- 4 years mean +/- SD) and eight young volunteers (CLcreat 134 +/- 18 ml/min, 25 +/- 8 years) received TMZ MR 35 mg b.i.d. (eight doses). Study 2: eight patients with severe renal failure (CLcreat 17 +/- 5 ml/min, 54 +/- 10 years), five patients with moderate renal failure (CLcreat 39 +/- 6 ml/min, 54 +/- 15 years) and eight volunteers (CLcreat 104 +/- 17 ml/min, 53 +/- 9 years) received TMZ MR 35 mg b.i.d. (patients: ten doses, volunteers: eight doses). Serial blood and urine samples were obtained following administration of the last dose in each study. TMZ plasma and urine concentrations were determined by gas chromatography (NPD-detector). The resulting data were analysed using standard non-compartmental pharmacokinetic methods. Results - Study 1: Elimination half-life of TMZ was significantly longer and renal clearance significantly lower in the elderly subjects. Study 2: In patients with either moderate or severe renal failure, exposure (AUC(0-24)) was significantly increased and renal clearance (CLR) was significantly decreased. Significant correlations were observed between CLcreat and CLR (r=0.94) and between CLcreat and AUC(0-24) (r=-0.94). Conclusion - With repeated administration of TMZ MR 35 mg b.i.d., a decrease in CLcreat is directly related to a decrease in CLR and results in an increase in exposure to TMZ. Copyright (C) 2003 John Wiley Sons, Ltd.