Objective:
The effect of trimethoprim, a potent organic cation transport inhibitor, on the pharmacokinetics (pk) of paliperidone extended-release tablets (paliperidone er), an organic cation mainly eliminated via renal excretion, was assessed.
Methods:
Open-label, two-period, randomized, crossover study in 30 healthy males. single dose of paliperidone er 6 mg was administered either alone on day 1 or day 5 during an 8-day treatment period of trimethoprim 200 mg twice daily. serial blood and urine samples were collected for pk and plasma protein binding of paliperidone and its enantiomers. the 90% confidence interval (ci) of ratios with/without trimethoprim for pk parameters of paliperidone and its enantiomers calculated.
Results:
Creatinine clearance decreased from 119 to 102 ml min(-1) with trimethoprim. addition of trimethoprim increased unbound fraction of paliperidone by 16%, renal clearance by 13%, auc(infinity) by 9%, and t((1/2)) by 19%. the 90% cis for ratios with/without trimethoprim were within the 80-125% range for c(max), auc(last), and renal clearance. for auc(infinity), 90% ci was 79.37-101.51, marginally below the lower bound of the acceptance range. paliperidone did not affect steady-state plasma concentrations of trimethoprim.
Conclusions:
No clinically important drug interactions are expected when paliperidone er is administered with organic cation transport inhibitors.