Pharmacokinetics and Safety of Risperidone Subcutaneous Implants in Stable Patients With Schizophrenia.

A subcutaneous risperidone implant (RI) formulation was developed to improve medication adherence in schizophrenia. Two phase 1 studies were conducted to evaluate the pharmacokinetics of RI in adult patients with schizophrenia. In study 1, all subjects were stable on 4 mg oral risperidone; subsequently, the first subject received 375 mg RI for 1 month, and the remaining subjects received 375 mg RI for 3 months. In study 2, all subjects were stable on oral risperidone 4 mg, 6 mg, or 8 mg and subsequently received RI 480 mg, 720 mg, or 960 mg, respectively, for 6 months. Blood samples were collected at prespecified time points. Various pharmacokinetic parameters were determined in both studies. In both studies risperidone total active moiety plasma concentrations following RI increased slowly, reached therapeutic levels within approximately 2 days, and remained relatively stable. In study 1, the average concentration for RI was 81.3% of the oral trough concentration and 27.5% of the oral peak concentration. In study 2, the steady-state concentration for RI was comparable to the oral trough concentration of the corresponding dose. Patient disease status remained stable with no major safety issues. RI may represent an alternative formulation for schizophrenia treatment with a lower peak-to-trough plasma drug ratio than oral risperidone.