Heinrich-Nols J, Schug B S, Evers G, Larsimont V, Elze M, Blume H H, Lee L S, Crawford F
Therapeutic Area CNS/General Drugs, Boehringer Ingelheim, Ingelheim am Rhein, Germany.
Int J Clin Pharmacol Ther. 1999 Mar;37(3):153-8.
Two extended release (ER) formulations of morphine sulphate (30 mg each), Oramorph SR (test) and a marketed reference formulation (MST Mundipharma Retardtabletten), were investigated for their relative bioavailability at steady-state:
The study was designed as a single-centre, open-label, two-period crossover, pharmacokinetic comparison in 28 healthy male volunteers and was completed in 23 subjects. The determination of morphine and its metabolite morphine-6-glucuronide in plasma was done by HPLC with electrochemical detection after solid-phase extraction.
Under steady-state conditions in the first dosing interval, mean maximum plasma concentrations for morphine were 19.1 ng/ml (CV% 41) for Oramorph SR 30 mg and 19.1 ng/ml (CV% 33) for MST-30 Mundipharma Retardtabletten. Geometric mean AUC(0-12) values were calculated as 108 ngxh/ml (CV% 40) for Oramorph SR 30 mg and as 118 ng x h/ml (CV% 30) for the reference formulation. The plasma concentrations of the major metabolite, morphine-6-glucuronide, were found to be generally in a higher range compared to the parent compound. The 90% confidence intervals of test to reference ratios calculated for all relevant parameters (AUC, C(max), PTF) for both the parent compound and morphine-6-glucuronide were all within the limits of 80 - 125%. The most frequent adverse events (AE > 10%) during Oramorph SR 30 mg treatment were headache (36%), dizziness (18%), nausea (21%), vomiting (21%) and pruritus (11%). During treatment with MST-30 Mundipharma Retardtabletten, the most frequent AEs were headache (29%), dizziness (13%), nausea (29%) and vomiting (29%).
The results demonstrate bioequivalence of Oramorph SR 30 mg and MST-30 Mundipharma Retardtabletten.
研究两种硫酸吗啡缓释制剂（每种30毫克），即Oramorph SR（试验制剂）和市售参比制剂（MST Mundipharma缓释片）在稳态时的相对生物利用度。
本研究设计为单中心、开放标签、两周期交叉试验，对28名健康男性志愿者进行药代动力学比较，最终23名受试者完成试验。血浆中吗啡及其代谢产物吗啡-6-葡萄糖醛酸苷的测定采用固相萃取后高效液相色谱电化学检测法。
在第一个给药间隔的稳态条件下，30毫克Oramorph SR的吗啡平均最大血浆浓度为19.1纳克/毫升（变异系数41%），MST - 30 Mundipharma缓释片为19.1纳克/毫升（变异系数33%）。30毫克Oramorph SR的几何平均AUC(0 - 12)值计算为108纳克·小时/毫升（变异系数40%），参比制剂为118纳克·小时/毫升（变异系数30%）。发现主要代谢产物吗啡-6-葡萄糖醛酸苷的血浆浓度总体上高于母体化合物。母体化合物和吗啡-6-葡萄糖醛酸苷所有相关参数（AUC、C(max)、PTF）的试验与参比比值的90%置信区间均在80 - 125%范围内。30毫克Oramorph SR治疗期间最常见的不良事件（发生率>10%）为头痛（36%）、头晕（18%）、恶心（21%）、呕吐（21%）和瘙痒（11%）。在MST - 30 Mundipharma缓释片治疗期间，最常见的不良事件为头痛（29%）、头晕（13%）、恶心（29%）和呕吐（29%）。
结果表明30毫克Oramorph SR与MST - 30 Mundipharma缓释片具有生物等效性。
