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• W3131856787 abstract "Abstract Purpose Peripherally acting μ-opioid receptor antagonists such as methylnaltrexone (MNTX, Relistor ® ) are indicated for the treatment of opioid-induced constipation (OIC). The structural properties unique to MNTX restrict it from traversing the blood-brain barrier (BBB); however, the BBB may become more permeable in patients with brain metastases. We investigated whether the presence of brain metastases in cancer patients compromises the central effects of opioids among patients receiving MNTX for OIC. Methods This post hoc analysis of pooled data from 3 randomized, placebo-controlled trials included cancer patients with OIC who received MNTX or placebo. Endpoints included changes from baseline in pain scores, rescue-free laxation (RFL) within 4 or 24 h of the first dose, and treatment-emergent adverse events (TEAEs), including those potentially related to opioid withdrawal symptoms. Results Among 356 cancer patients in the pooled population, 47 (MNTX n = 27; placebo n = 20) had brain metastases and 309 (MNTX n = 172; placebo n = 137) did not have brain metastases. No significant differences in current pain, worst pain, or change in pain scores from baseline were observed between patients treated with MNTX or placebo. Among patients with brain metastases, a significantly greater proportion of patients who received MNTX versus placebo achieved an RFL within 4 h after the first dose (70.4% vs 15.0%, respectively, p = 0.0002). TEAEs were similar between treatment groups and were generally gastrointestinal in nature and not related to opioid withdrawal. Conclusion Focal disruptions of the BBB caused by brain metastases did not appear to alter central nervous system penetrance of MNTX." @default.
• W3131856787 created "2021-03-01" @default.
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• W3131856787 date "2021-02-25" @default.
• W3131856787 modified "2023-10-16" @default.
• W3131856787 title "The influence of brain metastases on the central nervous system effects of methylnaltrexone: a post hoc analysis of 3 randomized, double-blind studies" @default.
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• W3131856787 doi "https://doi.org/10.1007/s00520-021-06070-7" @default.
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