Uptake and Intracellular Binding of Lipophilic Amine Drugs by Isolated Rat Hepatocytes and Implications for Prediction of in Vivo Metabolic Clearance
Drug Metabolism and Disposition, ISSN: 0090-9556, Vol: 34, Issue: 11, Page: 1829-1836
2006
- 51Citations
- 44Captures
Metric Options: CountsSelecting the 1-year or 3-year option will change the metrics count to percentiles, illustrating how an article or review compares to other articles or reviews within the selected time period in the same journal. Selecting the 1-year option compares the metrics against other articles/reviews that were also published in the same calendar year. Selecting the 3-year option compares the metrics against other articles/reviews that were also published in the same calendar year plus the two years prior.
Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
Citation Benchmarking is provided by Scopus and SciVal and is different from the metrics context provided by PlumX Metrics.
Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
Citation Benchmarking is provided by Scopus and SciVal and is different from the metrics context provided by PlumX Metrics.
Metrics Details
- Citations51
- Citation Indexes51
- 51
- CrossRef45
- Captures44
- Readers44
- 44
Article Description
The hepatic uptake of imipramine and propranolol was investigated after incubation with isolated rat hepatocytes over a wide concentration range (0.04–400 μM). The cell-to-medium concentration ratio ( K p ) was concentration-dependent and could be described using a two-site binding model incorporating a high affinity/low capacity site and a linear component for a site which was apparently not saturated. Maximum (at 0.04 μM) and minimum K p values (at 400 μM) were 360 and 280, and 110 and 70 for imipramine and propranolol, respectively. During these incubations, metabolism was inhibited using aminobenzotriazole (an irreversible inhibitor of cytochrome P450). Pretreatment of cells either by freeze-thawing or with saponin (which permeabilizes the plasma membrane) eliminated the saturable process. The saturable uptake process of imipramine was also inhibited by 18 other lipophilic amine drugs (including propranolol). This uptake component may involve membrane transporter(s), whereas the nonsaturable component probably represents partition into the phospholipid component of membranes. Propranolol was further investigated to determine the impact of high K p values on hepatocellular clearance. The area under the curve for propranolol concentrations in the total incubate (medium including the cells) from the depletiontime profile was substantially greater than the corresponding area under the curve for the drug concentration in the extracellular medium, and this difference approximated the nonsaturable uptake component. It is concluded that the clearance of propranolol in isolated hepatocytes is not rate-limited by hepatic uptake and is directly proportional to unbound drug concentration, being independent of the higher K p value.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S0090955624036468; http://dx.doi.org/10.1124/dmd.106.010413; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=33751100417&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/16882765; https://linkinghub.elsevier.com/retrieve/pii/S0090955624036468; https://dx.doi.org/10.1124/dmd.106.010413; https://dmd.aspetjournals.org/content/34/11/1829
Elsevier BV
Provide Feedback
Have ideas for a new metric? Would you like to see something else here?Let us know