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Controlled Clinical Trial
. 2020 Aug;81(5):564-572.
doi: 10.1002/ddr.21654. Epub 2020 Mar 4.

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

Nencho Nenchev  1 , Jiri Skopek  2 , Deepa Arora  3 , Abdus Samad  3 , Sigal Kaplan  4 , Mónika Domahidy  5 , Hanka de Voogd  6 , Stella Böhmert  7 , Rita S Ramos  8 , Shashank Jain  3
Affiliations
Controlled Clinical Trial

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

Nencho Nenchev et al. Drug Dev Res. 2020 Aug.

Abstract

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.

Keywords: age; pharmacokinetics; renal-impairment; safety; tolerability; trimetazidine.

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References

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