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Yasui-Furukori, N. et al.

Yasui-Furukori, Furukori, Nakagami, Saito, Inoue, Kaneko, Tateishi,

Steady-state pharmacokinetics of a new antipsychotic agent perospirone and its active metabolite, and its relationship with prolactin response.

The authors investigated steady-state pharmacokinetics of perospirone and its active metabolite hydroxyperospirone (ID-15036) and its prolactin response in 10 schizophrenic patients receiving 16 mg twice daily. Plasma concentrations of perospirone, hydroxyperospirone, and prolactin were monitored just before and up to 12 hours after the dosing. Thereafter, the dose was decreased to 8 mg twice daily in 8 patients, and drug concentrations were determined. The geometric means of peak concentration (Css(max)), time to Css(max) (tmax), area under the plasma concentration-time curve from 0 to 12 hours [AUC (0-12)], and elimination half-life at steady state were 8.8 ng/mL, 0.8 hours, 22.0 ng x h/mL, and 1.9 hours, respectively, for perospirone, and those of Css(max), tmax, and AUC (0-12) for hydroxyperospirone were 29.4 ng/mL, 1.1 hours, and 133.7 ng x h/mL, respectively. There were no differences in dose-normalized Css(max) or AUC (0-12) perospirone and hydroxyperospirone between 16 mg/day and 32 mg/day of perospirone. Changes in prolactin concentration from 1 to 2 hours after the dosing were parallel with drug concentrations, and almost normal ranges of prolactin concentration were observed before the morning dose despite steady state. The current study indicated that perospirone is rapidly absorbed and rapidly eliminated, which influences the prolactin response. The active metabolite hydroxyperospirone may play an important role in the antipsychotic effect because the plasma concentration of this metabolite is higher than that of the parent compound.[1]

References

Steady-state pharmacokinetics of a new antipsychotic agent perospirone and its active metabolite, and its relationship with prolactin response. Yasui-Furukori, N., Furukori, H., Nakagami, T., Saito, M., Inoue, Y., Kaneko, S., Tateishi, T. Therapeutic drug monitoring. (2004) [Pubmed]

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