Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA.
Int Clin Psychopharmacol. 2011 Jan;26(1):35-42. doi: 10.1097/YIC.0b013e32834093d1.
Oral-to-depot dose correspondence was explored in a 24-week study of olanzapine long-acting injection (LAI). Patients with schizophrenia stabilized on oral olanzapine of 10, 15, or 20 mg/day (n=1065) were randomized to continue their oral treatment or switch directly to a fixed dose of olanzapine LAI [(mg/weeks) 45/4, 150/2, 405/4, or 300/2] without oral supplementation. Six-month relapse rates for each LAI-dose group stratified by earlier oral dose were analyzed using a Cox proportional hazard model assessing risk of relapse relative to each oral dose. Relapse rates for the therapeutic LAI doses (≥ 150 mg) varied depending on earlier oral dose, ranging from 1.5% (patients switched from 10 mg/day to 300 mg/2 weeks) to 18.8% (patients switched from 20 mg/day to 150 mg/2 weeks). Switching from 10 mg/day to 405 mg/4 weeks produced a comparable risk of relapse as remaining on that oral dose [Hazard ratio (HR)=1.03]. Switching from 15 or 20 mg/day to 300 mg/2 weeks produced comparable risk of relapse as remaining on those oral doses (HR=0.68 and 1.13, respectively). Pharmacokinetic modeling was conducted to evaluate the resulting dosing recommendations. Findings suggest that patients can be switched directly from oral to olanzapine LAI without the need for oral supplementation and with a low risk of relapse when initiated on an appropriate LAI dose.
在一项为期 24 周的奥氮平长效注射剂（LAI）研究中探索了口服-注射剂量对应关系。1065 例稳定期精神分裂症患者接受 10、15 或 20mg/日的奥氮平口服治疗，随机分为继续口服治疗或直接转为固定剂量奥氮平 LAI[（mg/周）45/4、150/2、405/4 或 300/2]，无需口服补充。采用 Cox 比例风险模型分析每个 LAI 剂量组（按先前口服剂量分层）的 6 个月复发率，评估相对于每个口服剂量的复发风险。根据先前的口服剂量，治疗性 LAI 剂量（≥150mg）的复发率有所不同，范围为 1.5%（从 10mg/日转为 300mg/2 周的患者）至 18.8%（从 20mg/日转为 150mg/2 周的患者）。从 10mg/日转为 405mg/4 周的复发风险与继续口服该剂量相当[风险比（HR）=1.03]。从 15 或 20mg/日转为 300mg/2 周的复发风险与继续口服这些剂量相当（HR 分别为 0.68 和 1.13）。进行药代动力学建模以评估得出的剂量建议。结果表明，当以适当的 LAI 剂量起始时，患者可直接从口服转为奥氮平 LAI，无需口服补充，且复发风险较低。
