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

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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.

PubMed ID
12698499 [ View in PubMed
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Abstract

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 (CL(creat) 72+/-8 ml/min, 72+/-4 years mean+/-SD) and eight young volunteers (CL(creat) 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 (CL(creat.) 17+/-5 ml/min, 54+/-10 years), five patients with moderate renal failure (CL(creat.) 39+/-6 ml/min, 54+/-15 years) and eight volunteers (CL(creat.) 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 (CL(R)) was significantly decreased. Significant correlations were observed between CL(creat) and CL(R) (r=0.94) and between CL(creat) and AUC(0-24) (r=-0.94). Conclusion - With repeated administration of TMZ MR 35 mg b.i.d., a decrease in CL(creat) is directly related to a decrease in CL(R) and results in an increase in exposure to TMZ.

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