کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2486645 | 1114388 | 2011 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Transdermal and Oral dl-Methylphenidate-Ethanol Interactions in C57BL/6J Mice: Transesterification to Ethylphenidate and Elevation of d-Methylphenidate Concentrations
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Transdermal and Oral dl-Methylphenidate-Ethanol Interactions in C57BL/6J Mice: Transesterification to Ethylphenidate and Elevation of d-Methylphenidate Concentrations Transdermal and Oral dl-Methylphenidate-Ethanol Interactions in C57BL/6J Mice: Transesterification to Ethylphenidate and Elevation of d-Methylphenidate Concentrations](/preview/png/2486645.png)
چکیده انگلیسی
We tested the hypothesis that C57BL/6J mice will model human metabolic interactions between dl-methylphenidate (MPH) and ethanol, placing an emphasis on the MPH transdermal system (MTS). Specifically, we asked: (1) will ethanol increase d-MPH biological concentrations, (2) will MTS facilitate the systemic bioavailability of l-MPH, and (3) will l-MPH enantioselectively interact with ethanol to yield l-ethylphenidate (l-EPH)? Mice were dosed with MTS (14 of a 12.5Â cm2 patch on shaved skin) or a comparable oral dl-MPH dose (7.5Â mg/kg), with or without ethanol (3.0Â g/kg), and then placed in metabolic cages for 3Â h. MPH and EPH isomer concentrations in blood, brain, and urine were analyzed by gas chromatographic-mass spectrometry monitoring of N-(S)-prolylpiperidyl fragments. As in humans, MTS greatly facilitated the absorption of l-MPH in this mouse strain. Similarly, ethanol led to the enantioselective formation of l-EPH and to an elevation in d-MPH concentrations with both MTS and oral MPH. Although only guarded comparisons between MTS and oral MPH can be made due to route-dependent drug absorption rate differences, MTS was associated with significant MPH-ethanol interactions. Ethanol-mediated increases in circulating concentrations of d-MPH carry toxicological and abuse liability implications should this animal model hold for ethanol-consuming attention-deficit hyperactivity disorder patients or coabusers.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 100, Issue 7, July 2011, Pages 2966-2978
Journal: Journal of Pharmaceutical Sciences - Volume 100, Issue 7, July 2011, Pages 2966-2978
نویسندگان
Guinevere H. Bell, Andrew J. Novak, William C. III, Kennerly S. Patrick,