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

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.

Role of Trimetazidine in Ameliorating Endothelial Dysfunction: A Review

“…Trimetazidine is primarily eliminated unchanged, with over 60% excreted through urine [ 93 ]. Consequently, it is contraindicated in patients with chronic kidney disease [ 19 ], as its use in such individuals can significantly elevate plasma levels [ 94 ]. Additionally, trimetazidine may interact with medications prescribed for other coexisting conditions in patients with endothelial dysfunction, potentially compromising its efficacy or increasing the likelihood of adverse effects.…”

Effects of trimetazidine on heart failure with reduced ejection fraction and associated clinical outcomes: a systematic review and meta-analysis

“…With simple dose adjustments, it may be used in even lower eGFR ranges. 9 Furthermore, while the uptitration of current HF medication is frequently hindered by their haemodynamic (side)effects, no such effects exist with trimetazidine. Therefore, trimetazidine could serve as an interesting therapeutic adjunct in HF.…”

Single Ascending Dose Study to Assess Pharmacokinetic Linearity, Safety, and Tolerability of Trimetazidine - Modified Release in Healthy Human Subjects

“…1). The corresponding median time to C max (T max ) was comparable across the dose range investigated [ Following attainment of C max , the plasma concentration-time profile declined in a broadly mono-exponential fashion with a mean t 1/2 which was similar in each of the dose groups ranging from 6 Effect of a single dose (35, 70, and 105 mg) of TMZ-modified release on the PK parameters AUC (0-inf) , AUC (0-t) , and C max was analyzed. The slope estimates for all three parameters were less than 1, indic-ating that a less than dose-proportional increase in systemic exposure was observed with increasing dose (▶ Table 3).…”

“…Based on the results of current study, we also conducted a multiple-dose to evaluate the effect of age and renal impairment on the pharmacokinetics of trimetazidine (TMZ) in healthy elderly and renally-impaired subjects and to assess its safety and tolerability profile. Results of the multiple-dose study have been published elsewhere [6].…”