ClinPharm PK Consulting LLC, Bridgewater, NJ 08807, USA.
Adv Ther. 2010 Nov;27(11):846-58. doi: 10.1007/s12325-010-0074-x. Epub 2010 Oct 14.
Morphine sulfate and naltrexone hydrochloride extended release capsules, indicated for chronic moderate-to-severe pain, contain extended-release morphine pellets with a sequestered naltrexone core. If pellets are tampered by crushing, naltrexone is released to reduce morphine-induced effects that appeal to opioid abusers. The primary objective of this study was to assess single-dose relative bioavailability of morphine when morphine sulfate and naltrexone hydrochloride extended release capsules were taken under fed and fasting conditions and when pellets were sprinkled on apple sauce.
This was a single-center, randomized, open-label study in 36 healthy adult volunteers. Subjects took a 100-mg morphine sulfate and naltrexone hydrochloride extended release capsule intact with 240 mL water, under fed and fasted conditions, and when the capsule was opened and pellets were sprinkled over apple sauce and consumed without chewing; each treatment was separated by a 14-day washout. Plasma samples were collected just before dosing through 72 hours postdose for pharmacokinetic analyses of morphine, and through 168 hours postdose for naltrexone and its major metabolite 6-β-naltrexol.
Morphine bioavailability was similar for all treatments. There was a lack of sprinkle effect (sprinkle vs. whole, fasted); 90% confidence intervals (CIs) of ratios of log-transformed least squares means for area under the plasma concentration-time curve (AUC) and peak plasma concentration (C(max)) fell within 80%-125% boundaries. For the food effect, 90% CIs were within the boundaries for AUC, but C(max) was reduced and time to C(max) was delayed by 2.5 hours under fed conditions. Naltrexone remained sequestered under all treatment conditions with only trace systemic exposure.
Results indicated that morphine sulfate and naltrexone hydrochloride extended release capsules can be administered without regard to meals, and contents can be sprinkled over apple sauce and consumed without chewing by patients with difficulty swallowing.
硫酸吗啡和盐酸纳曲酮缓释胶囊，用于治疗慢性中重度疼痛，含有缓释吗啡丸和隔离的纳曲酮核心。如果丸剂被压碎，纳曲酮会释放出来，减少对阿片类药物滥用者有吸引力的吗啡作用。这项研究的主要目的是评估在进食和禁食条件下以及将丸剂撒在苹果酱上时，硫酸吗啡和盐酸纳曲酮缓释胶囊单次给药的相对生物利用度。
这是一项在 36 名健康成年志愿者中进行的单中心、随机、开放标签研究。受试者用水服下 100mg 硫酸吗啡和盐酸纳曲酮缓释胶囊，分别在进食和禁食条件下，以及打开胶囊并将丸剂撒在苹果酱上而无需咀嚼的情况下服用；每种处理方法之间有 14 天的洗脱期。在给药前至 72 小时后进行吗啡的药代动力学分析，以及在 168 小时后进行纳曲酮及其主要代谢物 6-β-纳曲醇的药代动力学分析。
所有治疗方法的吗啡生物利用度相似。没有撒粉效应（撒粉与整片，禁食）；对数转换最小二乘均值比值的 90%置信区间（CI）在 80%-125%范围内。对于食物效应，AUC 的 90%CI 在边界内，但 C(max)降低，并且在进食条件下 C(max)的时间延迟了 2.5 小时。在所有治疗条件下，纳曲酮都被隔离，只有痕量的系统暴露。
结果表明，硫酸吗啡和盐酸纳曲酮缓释胶囊可以不考虑进食时间服用，并且可以将丸剂撒在苹果酱上，无需咀嚼即可服用。
