Pharmacokinetic profile of long-acting injectable risperidone at steady-state: comparison with oral administration.
The single dose pharmacokinetic profiles of long-acting injectable (LAI) risperidone and oral risperidone were extrapolated to steady-state. Plasma concentrations of the active moiety (unchanged risperidone + 9-hydroxy-risperidone) were measured by radioimmunoassay up to 72 h after a single oral 1 mg dose of risperidone in healthy volunteers (n = 12), and up to 84 days after a single intramuscular injection of 50 mg LAI risperidone in schizophrenic patients (n = 26). These data were projected to multiple dose regimens (4 mg/day for the oral formulation and 50 mg every 2 weeks for LAI formulation) using the software package WinNonlin, and average steady-state pharmacokinetic profiles were predicted. The most interesting results, obtained at steady-state, were a lower predicted peak plasma level (46 vs. 62 ng/ml) and a lower predicted degree of fluctuation between Cssmax and Cssmin (53 vs 145%) with LAI compared to oral administration, which is in line with actual steady state data on LAI risperidone. In conclusion, the pharmacokinetic profile of LAI risperidone administered every 2 weeks ensures a steady-state profile with concentrations falling in the interval observed with an equivalent oral dose but with lower and less fluctuations (i.e. 1/2 weeks vs 1/day).
Mannaert
E
E
Johnson & Johnson Pharmaceutical Research & Development, Janssen Pharmaceutica NV, Beerse, Belgium.
Vermeulen
A
A
Remmerie
B
B
Bouhours
P
P
Levron
J C
JC
D000284:Administration, Oral; D000328:Adult; D001480:Basal Ganglia Diseases / Q000175:diagnosis / Q000453:epidemiology; D003692:Delayed-Action Preparations; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D018967:Risperidone / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy*
D003692:Delayed-Action Preparations; D018967:Risperidone