Kapil Ram P, Cipriano Alessandra, Wen Warren, Yu Lynch Shau, He Ellie, Colucci Salvatore V, Harris Stephen C
Purdue Pharma LP, Stamford, Connecticut.
Purdue Pharma LP, Stamford, Connecticut.
Clin Ther. 2016 Feb;38(2):302-14. doi: 10.1016/j.clinthera.2015.12.003. Epub 2015 Dec 31.
The purpose of this study was to evaluate the pharmacokinetics (PK) and 24-hour analgesic effectiveness of once-daily, single-entity, extended-release hydrocodone (HYD) with abuse-deterrent properties.
Four studies were included. Three open-label PK studies had the following designs: single-dose, 5-treatment, 4-period, crossover, dose-proportionality study; HYD 120 mg for 5 days (steady-state study 1); 2-treatment, 2-period, multiple-dose crossover study assessing the relative bioavailability of HYD 30 mg and hydrocodone 7.5 mg/ibuprofen 200 mg administered every 6 hours (steady-state study 2). A long-term, open-label study assessed the safety and effectiveness of HYD 20 to 120 mg in patients during a 52-week maintenance period.
Thirty-one, 25, and 22 healthy subjects completed the dose-proportionality study, steady-state study 1, and steady-state study 2, respectively, while 410 patients with moderate to severe chronic nonmalignant and non-neuropathic pain completed the long-term effectiveness study. Mean systemic exposure and peak plasma concentration were dose proportional after administration of single doses of HYD 20 to 120 mg. Pharmacokinetic profiles were comparable at day 1 and day 5 after administration of HYD 120 mg once daily. Once-daily HYD 30 mg was associated with lower-fluctuating plasma hydrocodone concentrations compared with immediate-release hydrocodone 7.5 mg/ibuprofen 200 mg administered every 6 hours. In the long-term study, pain control was consistent over the 24-hour dosing interval.
Once-daily HYD exhibits linear, dose-proportional PK properties and is associated with a lower variability in plasma hydrocodone concentrations when compared with an immediate-release hydrocodone combination product. Notably, analgesia provided by HYD is sustained during the 24-hour dosing interval. ClinicalTrials.gov identifier: NCT01400139 (Study 4).
本研究旨在评估具有滥用威慑特性的每日一次单实体缓释氢可酮（HYD）的药代动力学（PK）及24小时镇痛效果。
纳入四项研究。三项开放标签PK研究设计如下：单剂量、5种治疗方案、4周期、交叉、剂量比例研究；120毫克HYD服用5天（稳态研究1）；2种治疗方案、2周期、多剂量交叉研究，评估每6小时服用一次的30毫克HYD与7.5毫克氢可酮/200毫克布洛芬的相对生物利用度（稳态研究2）。一项长期开放标签研究评估了20至120毫克HYD在患者52周维持期的安全性和有效性。
分别有31名、25名和22名健康受试者完成了剂量比例研究、稳态研究1和稳态研究2，同时有410名中度至重度慢性非恶性和非神经性疼痛患者完成了长期有效性研究。单次服用20至120毫克HYD后，平均全身暴露量和血浆峰浓度与剂量成比例。每日一次服用120毫克HYD后第1天和第5天的药代动力学特征具有可比性。与每6小时服用一次的速释型7.5毫克氢可酮/200毫克布洛芬相比，每日一次服用30毫克HYD的血浆氢可酮浓度波动较小。在长期研究中，24小时给药间隔内的疼痛控制保持一致。
每日一次服用HYD具有线性、剂量成比例的PK特性，与速释型氢可酮复方制剂相比，其血浆氢可酮浓度变异性较低。值得注意的是，HYD提供的镇痛作用在24小时给药间隔内持续存在。ClinicalTrials.gov标识符：NCT01400139（研究4）。
