کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2484287 | 1114305 | 2016 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Development of a Novel Lung Slice Methodology for Profiling of Inhaled Compounds
ترجمه فارسی عنوان
توسعه یک روش ریز برای تشخیص ترکیبات استنشاقی
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کلمات کلیدی
PBPK1-methyl-4-phenylpyridiniumMPP+ - MPP +Pulmonary drug delivery - تحویل داروی ریویDistribution - توزیعPulmonary - ریهpharmacodynamic - فارماکودینامیکPharmacokinetics - فارماکوکینتیکpharmacokinetic - فارماکوکینتیکPhysiologically based pharmacokinetic - فارماکوکینتیک مبتنی بر فیزیولوژیlactate dehydrogenase - لاکتات دهیدروژناز LDH - لاکتات دهیدروژناز به صورت مختصر شده LDH Tissue partition - پارتیشن بافت
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
چکیده انگلیسی
The challenge of defining the concentration of unbound drug at the lung target site after inhalation limits the possibility to optimize target exposure by compound design. In this study, a novel rat lung slice methodology has been developed and applied to study drug uptake in lung tissue, and the mechanisms by which this occurs. Freshly prepared lung slices (500 μm) from drug-naive rats were incubated with drugs followed by determination of the unbound drug volume of distribution in lung (Vu,lung), as the total concentration of drug in slices divided by the buffer (unbound) concentration. Vu,lung determined for a set of inhaled drug compounds ranged from 2.21 mL/g for salbutamol to 2970 mL/g for dibasic compound A. Co-incubation with monensin, a modulator of lysosomal pH, resulted in inhibition of tissue uptake of basic propranolol to 13%, indicating extensive lysosomal trapping. Partitioning into cells was particularly high for the cation MPP+ and the dibasic compound A, likely because of the carrier-mediated transport and lysosomal trapping. The results show that different factors are important for tissue uptake and the presented method can be used for profiling of inhaled compounds, leading to a greater understanding of distribution and exposure of drug in the lung.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 105, Issue 2, February 2016, Pages 838-845
Journal: Journal of Pharmaceutical Sciences - Volume 105, Issue 2, February 2016, Pages 838-845
نویسندگان
Erica Bäckström, Anders Lundqvist, Elin Boger, Petter Svanberg, Pär Ewing, Margareta Hammarlund-Udenaes, Markus Fridén,