Abstract: Objectives To identify the determinants of the trough steady-state concentration/dose ratio (C_min/D) of sulpiride, and detect the risk factors for hyperprolactinemia(HPRL) as well as extra pyramidal symptoms (EPS) after sulpiride administration based on therapeutic drug monitoring(TDM). Methods Hospitalized patients who underwent TDM in Beijing Anding Hospital between September 1, 2018 and February 28, 2023 were included. Such basic information as gender, age, body mass index (BMI), history of smoking and serum creatine levels was retrieved from the medical record system. Data on dosage, comedication and adverse drug reactions was also recorded. SPSS 26.0 was used for statistical analysis. Results One hundred and thirteen patients with steady-state concentrations determined by TDM were included. The daily dosage of sulpiride was 0.4 (0.3, 0.8) g·d^-1, trough steady-state concentration (C_min) 374.80 (210.64, 656.58) ng·mL^-1,and the trough steady-state concentration/dose ratio (C_min/D) was 0.83 (0.59, 1.10) ng·mL^-1·mg^-1·d. Multiple linear regression analysis suggested that gender and age had significant effects on Cmin/D (P<0.05). The most common adverse reactions were HPRL and EPS. The combination of TCAs/SSRIs increased the risk of EPS (P<0.05), and gender was identified as a risk factor for HPRL(P<0.05). Conclusion The Cmin of sulpiride is dose related, and C_min/D is higher among females than among males, and higher among minors than among adults and geriatric patients. Concomitant use of TCAs/SSRIs with sulpiride requires caution due to the EPS risk, and prolactin levels should be closely monitored when sulpiride is administered to female patients.

Key words: Sulpiride, Therapeutic Drug Monitoring (TDM), Trough Steady-State Concentration, Dose, Extra Pyramidal Symptoms (EPS), Hyperprolactinemia (HPRL), Risk Factors