Effect of age and renal impairment on the pharmacokinetics and safety of trimetazidine: An open-label multiple-dose study.

This study evaluated the effect of age and renal impairment on pharmacokinetics of trimetazidine (TMZ) in healthy elderly and renally impaired subjects and assess safety and tolerability. In this open-label, multi-dose study, 73 subjects were divided into six treatment groups: (1) 55-65 years; (2) 66-75 years; (3) >75 years (dosing for groups 1-3 [healthy]: B.D. for 4 days), (4) mild renally impaired (dosed B.D. for 8 days); (5) moderate renally impaired (dosed O.D. for 8 days); and (6) severe renally impaired-no dialysis (dosed once every 48 h for 8 days). Blood and urine samples were collected and analyzed. The geometric least squares mean ratios for; Group 2 and 1 of AUC(0-τ)ss was 112.2 (90% CI; 92.0-136.8) and Cmax,ss was 109.9 (89.6-134.8), Group 3 and 1 of AUC(0-τ),ss was 140.5 (115.9-170.3) and Cmax,ss was 137.8 (112.9-168.2), Group 4 and 1 of AUC(0-τ),ss was 114.2 (90.3-144.4) and Cmax,ss was 120.8 (92.5-157.8), Group 5 and 1 of; AUC(0-τ),ss was 213.0 (153.1-296.3) and Cmax,ss was 123.3 (92.2-164.7) and Group 6 and 1 of AUC(0-τ),ss was 247.4 (197.8-309.6) and Cmax,ss was 95.6 (73.0-125.1). Significant increase in systemic exposure of TMZ was observed in subjects; over 75 year's age and renally impaired compared to healthy subjects. TMZ was safe and well-tolerated.

Cardiovascular risk with SCORE system in patients with different degree of renal function impairment.

A risk prediction system, Systematic Coronary Risk Evaluation, that is based on European studies has been developed and recommended to define absolute 10-year risk of a fatal cardiovascular event and mortality. The aim of the study was to compare cardiovascular risk calculated with SCORE system at patients with different degree of renal impairment. The study included 90 patients divided in 4 groups: 1st group=30 patients without renal failure, 2nd group=25 patients with CRF in predialysis stage, 3rd group=19 hemodialysis non-diabetic patients and 4th group=16 hemodialysis diabetics patients. SCORE was calculated from age, sex, systolic blood pressure, smoking and cholesterol levels. There were no significant differences in age and blood pressure in four examined groups. The incidence of smokers and cholesterol level were higher in predialysis patients. The highest SCORE was calculated in predialysis patients: 1st group: 2.5+/-1.8; 2nd group: 5.3+/-4.3, 3rd group: 3.7+/-1.1 and 4th group: 4.06+/-4. We supposed that traditional risk factors from SCORE risk system are suitable to explain the cardiovascular risk and mortality in all population but underestimates cardiovascular risk of high-risk groups like patients with chronic renal disease.