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 (CLcreat 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 (AUC0–24) 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 AUC0–24 (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 © 2003 John Wiley & Sons, Ltd.