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(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.
Thyssen
An
A
Johnson & Johnson Pharmaceutical Research & Development, Beerse, Belgium. athyssen@its.jnj.com
Cleton
Adriaan
A
Talluri
Krishna
K
Leempoels
Jos
J
Janssens
Luc
L
Boom
Sandra
S
Eerdekens
Marielle
M
D000328:Adult; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D019540:Area Under Curve; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D016503:Drug Delivery Systems; D004347:Drug Interactions; D004562:Electrocardiography / Q000379:methods; D005493:Folic Acid Antagonists / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007555:Isoxazoles / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008297:Male; D008875:Middle Aged; D000068882:Paliperidone Palmitate; D011743:Pyrimidines / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D016037:Single-Blind Method; D013997:Time Factors; D014295:Trimethoprim / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D055815:Young Adult
D014150:Antipsychotic Agents; D005493:Folic Acid Antagonists; D007555:Isoxazoles; D011743:Pyrimidines; D014295:Trimethoprim; D000068882:Paliperidone Palmitate