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Separation and Determination of methylnaltrexone in Human Plasma Samples After Oral Administration by HPLC Coupled with Electrochemical Detection

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Chemical Research in Chinese Universities 2005年第3期21卷 268-273页

作者： WANGAn-bao JosephF.Foss YUANChun-su JoachimOsinski DepartmentofAnesthesiaandCriticalCare TheUniversityofChicagoChicagoIL60637USA DepartmentofAnesthesiaandCriticalCare TheUniversityofChicagoChicagoIL60637USA／／ShanghaiInstituteofCeramicsChineseAcademyofSciencesShanghai200050P.R.China

A high performance liquid chromatography(HPLC) method coupled with electrochemical detection and solid phase extraction is described for the separation and determination of methylnaltrexone(MNTX), a quaternary opioid antagonist, in human clinical plasma samples after oral administration. Linearity of the standard curve for MNTX was found in the range of 4.0_150 ng/mL and was statistically conformed. The correlation coefficient(r2) and calibration equation obtained from linear regression analysis are 0.9999 and Y=54.27X-0.22, where Y and X represent the peak area and concentration of MNTX, respectively. The detection limit of MNTX under the present experimental conditions is 2.0 ng/mL by estimating at a ratio of 3 of signal to noise. The mean recovery of MNTX in human plasma is higher than 97%. The analytical method was applied to the pharmacokinetic determination of MNTX after single dose oral administration. These data demonstrate that the change of MNTX plasma concentration versus time is obvious. MNTX level of plasma reaches to a plateau between 45 to 120 minutes and then falls slowly. The content of MNTX in plasma sample maintains at an obviously detectable level after twelve hours of oral administration. The pharmacokinetic parameters for a single dose of 19.2 mg/kg in plasma are c_~max =206.42(±16.53) ng/mL and t_~max =60 min.

关键词： Liquid chromatography Electrochemical detection methylnaltrexone Pharmaceutical Serum Biological analysis

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新一代外周阿片受体拮抗剂——methylnaltrexone(MNTX,甲基纳曲酮)

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疼痛 2003年第1期11卷 17-19页

作者：李绍清薛张纲复旦大学附属中山医院麻醉科 200032

麻醉性镇痛剂是一种强镇痛剂,在围手术期及晚期癌痛患者中常广泛应用。在美国,每年约有1.7亿张阿片剂的处方,它们在减轻患者痛苦的同时也带来了许多副作用。有许多机构曾经和正在开发阿片剂的拮抗剂,以阻断阿片剂的副反应。现临床常用... 详细信息

麻醉性镇痛剂是一种强镇痛剂,在围手术期及晚期癌痛患者中常广泛应用。在美国,每年约有1.7亿张阿片剂的处方,它们在减轻患者痛苦的同时也带来了许多副作用。有许多机构曾经和正在开发阿片剂的拮抗剂,以阻断阿片剂的副反应。现临床常用的拮抗剂有:纳络酮(naloxone)和纳曲酮(naltrexone)。

关键词：阿片剂不良反应外周阿片受体拮抗剂 methylnaltrexone 分子结构给药方法

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Management of constipation in the elderly: Emerging therapeutic strategies

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World Journal of Gastroenterology 2008年第33期14卷 5226-5227页

作者： Shailendra Kapoor Department of Family Medicine University of Illinois at ChicagoChicago IL 60612 United States

A number of new, novel strategies for managing constipation in the elderly have emerged over the past few years. Prucalopride is one such new agent that is highly effi cacious in managing chronic constipation. In fact, Camilleri et al in a recent study reported that the average number of bowel movements increased by at least one in nearly 47% of the patients who were administered a dose of 4 mg. Lubiprostone is another new agent recently approved by the FDA that shows efficacy in managing the symptoms of constipation. Neostigmine has also been successfully used for the management of recalcitrant constipation. Most of these studies have used subcutaneous neostigmine. Symbiotic yogurt containig components, such as Bifidobacterium and fructoligosaccharide, have also been recently shown to be highly effective in improving symptoms of constipation. Elderly patients especially those in hospices and nursing homes are often on opiods for pain management. Constipation secondary to opioid use is extremely common in nursing homes. Subcutaneous methylnaltrexone has recently been shown to be highly effective in the management of opioid-related constipation, and was recently approved by the FDA. Sacral nerve stimulation is another emerging strategy. A recent analysis by Mowatt et al supports the eff icacy of this technique. Botulinum toxin is another agent that has already been successfully used for the management of chronic, refractory constipation in children and may be very effective for elderly constipation. Further larger studies are needed to confi rm the fi ndings noted in these studies. Constipation is clearly a major issue in the elderly and these new, emerging strategies will hopefully improve the quality of life and relieve the symptoms of constipation in this population.

关键词： Constipation Prucalopride Lubiprostone Neostigmine methylnaltrexone

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