Pharmacokinetics, pharmacodynamics and safety of a single-dose long-acting Risperidone injection in Chinese patients with schizophrenia

doi:10.5246/jcps.2021.03.016

Abstract

Abstract:

In the present study, we aimed to determine the pharmacokinetics (PK), pharmacodynamics (PD), adverse events (AEs), and their relationships in Chinese patients with schizophrenia after a single dose of long-acting risperidone. Schizophrenic patients (six females and seven males) were enrolled in this study. Serial blood samples were collected after drug administration during 63 d, and the drug concentrations were analyzed by LC-MS/MS. Safety and tolerance were evaluated by monitoring the AEs, changes in clinical laboratory results, 12-lead ECG, vital signs, physical examination, and injection-site reactions. The extrapyramidal symptoms were evaluated using the ESRS. Efficacy was evaluated by the PANSS and BPRS. Twelve out of the 13 participants completed the trial. There were few clinically meaningful changes in mean clinical laboratory values, vital signs, or ECG parameters, except for the prolactin level and body weight. There were no serious AEs, and those observed were reversible. Significant clinical improvements in PANSS and PANSS-derived BPRS total scores were observed. The mean (standard deviation, coefficient of variation) values for these PK parameters were as follows: C_max, 8.954 (8.059, 90.0%) ng/mL; area under the curve AUC_0–t, 2453 (1156, 47.1%) ng?h/mL; AUC_0–∞, 2472 (1160, 46.9%) ng?h/mL; t_max, 830.0 (min: 744.0, max: 984.0, 11.8%) h; and t_1/2, 68.56 (10.77, 15.7%) h. The PK characteristics of long-acting risperidone showed a high level of inter-individual variation, while there were no clear correlations between PK, efficacy and AEs among the patients in the present study.

Key words: Long-acting risperidone injection, Single-dose, Pharmacokinetics, LC-MS/MS, Chinese schizophrenic patients

Supporting:

Xiaojiao Li, Shuxin Luan, Hong Zhang, Hongquan Wan, Hong Chen, Chengjiao Liu, Chang Liu, Yanhua Ding. Pharmacokinetics, pharmacodynamics and safety of a single-dose long-acting Risperidone injection in Chinese patients with schizophrenia[J]. Journal of Chinese Pharmaceutical Sciences, 2021, 30(3): 206-217.

Figures/Tables 10

Table 1. Demographic data and baseline characteristics of patients (six females and seven males).

Table 2. PK parameters of risperidone long-acting injection (25 mg), in comparison with published data[9].

Table 3. Total PANSS scores at various time points (baseline, day 30 and day 63).

Table 4. Changes in PANSS and BPRS scores from baseline to day 63 (n = 11).

Table 5. Changes in prolactin and weight from baseline to day 63 (n = 12).

Table 6. Incidence of AEs (n = 13).

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