کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
328170 543091 2007 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Blood–brain barrier penetration and pharmacokinetics of amitriptyline and its metabolites in p-glycoprotein (abcb1ab) knock-out mice and controls
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی روانپزشکی بیولوژیکی
پیش نمایش صفحه اول مقاله
Blood–brain barrier penetration and pharmacokinetics of amitriptyline and its metabolites in p-glycoprotein (abcb1ab) knock-out mice and controls
چکیده انگلیسی

In earlier studies with P-gp (abcb1) knock-out mice, we showed that P-gp exports the antidepressants citalopram, paroxetine, venlafaxine and amitriptyline and its metabolites across the blood–brain barrier, thereby reducing cerebral bioavailability of some substances up to 9 times. The present study investigated the pharmacokinetics of amitriptyline and whether abcb1ab double knock-out mice metabolize amitriptyline and its metabolites differently. P-gp knock-out mice and controls received a s.c. injection of 10 μg amitriptyline/g of body weight. The animals were sacrificed after 30, 60, 120 and 240 min and concentrations of amitriptyline and its metabolites were measured with HPLC in brain, plasma, liver, kidney, spleen, lung, muscle, fat and ovaries. Cerebral concentrations of amitriptyline and its metabolites were higher in P-gp-deficient mice compared to controls. No significant group effect was found for spleen, liver, lung, kidney and fat tissue. The results of our study indicate that amitriptyline and its metabolites are substrates of P-gp. Overall pharmacokinetics between knock-outs and controls were very similar. This confirms the validity of the P-gp knock-out model and allows for a continued research of the interactions between P-gp, the blood–brain barrier and CNS substances such as antidepressants, neuroleptics and others.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Psychiatric Research - Volume 41, Issues 1–2, January–February 2007, Pages 179–188
نویسندگان
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