The pharmacokinetics of immediate (IR) and modified release (MR) trimetazidine (TMZ) in dogs and pigs, have been compared under single dose conditions, then predicted at steady-state under conditions mimicking an actual human pharmacokinetic study. In both animal species, the MR tablet has demonstrated sustained release properties, as assessed by delayed time to peak and increased mean absorption times. Multiple dose simulations in dogs revealed a delayed time to peak (3.0 vs. 1.0 h), a decrease in peak plasma concentration (544 vs. 659 microg/L), an increase in trough concentrations (115 vs. 63 microg/L), a decrease in peak-trough fluctuation (141 vs. 193%), and an increase in plateau time (5.5 vs. 4.9 h). Qualitatively similar changes were simulated in pigs. These properties have then been verified in humans where a TMZ MR 35 mg b.i.d regimen did provide similar total exposure, increased plateau time (11 vs. 4 h), decreased peak-trough fluctuation (86 vs. 121%), a 31% increase in trough concentrations, and no increase in inter-individual variability as compared to a TMZ IR 20 mg t.i.d. regimen. Furthermore, the TMZ MR 35 mg b.i.d. regimen is likely to result in improved patient compliance and better patient anti-ischemic protection in the early morning.