Mannaert E, Vermeulen A, Remmerie B, Bouhours P, Levron J C
Johnson & Johnson Pharmaceutical Research & Development, Janssen Pharmaceutica NV, Beerse, Belgium.
Encephale. 2005 Sep-Oct;31(5 Pt 1):609-15. doi: 10.1016/s0013-7006(05)82420-0.
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).
长效注射用利培酮和口服利培酮的单剂量药代动力学曲线被外推至稳态。在健康志愿者（n = 12）单次口服1 mg利培酮后长达72小时，以及在精神分裂症患者（n = 26）单次肌内注射50 mg长效注射用利培酮后长达84天，通过放射免疫分析法测定活性部分（未改变的利培酮 + 9 - 羟基利培酮）的血浆浓度。使用WinNonlin软件包将这些数据推算至多剂量方案（口服制剂为4 mg/天，长效注射用制剂为每2周50 mg），并预测平均稳态药代动力学曲线。在稳态时获得的最有趣结果是，与口服给药相比，长效注射用制剂预测的血浆峰浓度较低（46对62 ng/ml），预测的Cssmax和Cssmin之间的波动程度较低（53对145%），这与长效注射用利培酮的实际稳态数据一致。总之，每2周给药一次的长效注射用利培酮的药代动力学曲线确保了稳态曲线，其浓度落在等效口服剂量观察到的区间内，但波动更低且更小（即1/2周对1/天）。
