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Effect of age and renal impairment on the pharmacokinetics and safety of trimetazidine: An open‐label multiple‐dose study
Author(s) -
Nenchev Nencho,
Skopek Jiri,
Arora Deepa,
Samad Abdus,
Kaplan Sigal,
Domahidy Mónika,
Voogd Hanka,
Böhmert Stella,
Ramos Rita S.,
Jain Shashank
Publication year - 2020
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.21654
Subject(s) - medicine , pharmacokinetics , tolerability , dosing , trimetazidine , urine , urology , area under the curve , adverse effect
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 C max,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 C max,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 C max,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 C max,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 C max,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.