Multiple dose pharmacokinetics of risperidone and 9-hydroxyrisperidone in Chinese female patients with schizophrenia.
OBJECTIVE
To study the multiple dose clinical pharmacokinetics of risperidone and its main active metabolite, 9-hydroxyrisperidone, in Chinese female patients with schizophrenia.


METHODS
The subjects were 23 Chinese female inpatients aged 18-65 years who met the CCMD-III (third revision of the Chinese Criteria of Mental Disorders) criteria for schizophrenia. Subjects were tested after 17 d of treatment with 2 mg risperidone twice daily. Plasma concentrations of risperidone and 9-hydroxy-risperidone were assayed by using validated high performance liquid chromatography-mass spectrometry (HPLC-MS) methods.


RESULTS
Risperidone was rapidly absorbed (Tmax was 1.6 h) and its T1/2 in plasma was short (3.2 h). 9-hydroxy-risperidone was quickly metabolized from the parent drug with a mean Tmax of 2.5 h. It had a long half-life of 24.7 h. The C(ss)(av) of risperidone and 9-hydroxy-risperidone were 36.9+/-33.1 and 110.6+/-30.5 microg x h x L(-1), respectively, and the AUC(ss)0-12 were 443.2+/- 397.4 and 1327.2+/- 402.3 microg x h x L(-1), respectively. CL/F and V/F of risperidone were 8.7+/- 6.2 L/h and 34.1+/- 24.3 L, respectively. Interindividual variations for pharmacokinetic parameters were quite large for risperidone. All 23 subjects experienced high prolactin levels when treated with risperidone. However there was no correlation between prolactin level and the concentration of risperidone, 9-hydroxy-risperidone, or the active moiety.


CONCLUSIONS
Risperidone showed large interindividual variations in pharmacokinetics. Administration of risperidone resulted in high serum prolactin levels. The results indicate that systemic exposure to risperidone and 9-hydroxy-risperidone in female Chinese schizophrenic patients is higher relative to published data for white Caucasian patients. Larger studies regarding the PK/PD relationship may be required to develop a reasonable clinical dosage regimen for Chinese female patients.
Clinical Pharmacy Research Institute, Xiangya Second Hospital, Central South University, Changsha 410011, China.
Zhi-ling
ZL
Zhou
Xin
X
Li
Huai-yan
HY
Peng
Xi-yong
XY
Yu
Ming
M
Yang
Feng-li
FL
Su
Feng
F
Wang
Rong-hua
RH
Zhu
Chun-yu
CY
Deng
Qiu-xiong
QX
Lin
Chuan-yue
CY
Wang
Wen-biao
WB
Li
Shu-guang
SG
Lin
Huan-de
HD
Li
D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D044466:Asian People; D002681:China; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008875:Middle Aged; D000068882:Paliperidone Palmitate; D011743:Pyrimidines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018967:Risperidone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012559:Schizophrenia / Q000378:metabolism*
D014150:Antipsychotic Agents; D007555:Isoxazoles; D011743:Pyrimidines; D018967:Risperidone; D000068882:Paliperidone Palmitate