The influence of hepatic impairment on the pharmacokinetics of paliperidone.
OBJECTIVE
This study assessed the impact of hepatic impairment on the pharmacokinetics (PK) of paliperidone and its enantiomers.


METHODS
A single 1 mg dose of paliperidone immediate-release (IR) was administered to subjects with moderate hepatic impairment (n = 10) and demographically matched individuals with normal hepatic function (n = 10).


RESULTS
Plasma protein binding was lower in hepatically impaired subjects resulting in a 27% higher unbound fraction of paliperidone compared with healthy individuals. After correcting for the difference in plasma protein binding, unbound exposures were comparable between groups. All other PK parameters were similar between the two groups. Paliperidone IR was equally well tolerated in both groups.


CONCLUSIONS
The impact of moderate hepatic impairment on paliperidone PK is not considered clinically relevant as the PK profile of unbound paliperidone is similar for subjects with moderate hepatic impairment and those with normal hepatic function. Dosage adjustments of paliperidone are not required in subjects with mild or moderate hepatic impairment.
Boom
S
S
Johnson & Johnson Pharmaceutical Research & Development, Beerse, Belgium.
Thyssen
A
A
Crauwels
H
H
Molz
K H
KH
Cleton
A
A
Janssens
L
L
Talluri
K
K
Eerdekens
M
M
D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D001798:Blood Proteins / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000009:adverse effects / Q000493:pharmacokinetics*; D008107:Liver Diseases / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D000068882:Paliperidone Palmitate; D011485:Protein Binding; D011743:Pyrimidines / Q000009:adverse effects / Q000493:pharmacokinetics*
D014150:Antipsychotic Agents; D001798:Blood Proteins; D007555:Isoxazoles; D011743:Pyrimidines; D000068882:Paliperidone Palmitate