No pharmacokinetic interaction between paliperidone extended-release tablets and trimethoprim in healthy subjects

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∞ by 9%, and t½ by 19%. The 90% CIs for ratios with/without trimethoprim were within the 80–125% range for Cmax, AUClast, and renal clearance. For AUC∞, 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. Copyright © 2009 John Wiley & Sons, Ltd.