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10.1111/bcp.12996 http://scihub22266oqcxt.onion/10.1111/bcp.12996 C5338106!5338106!27135195     free     free     free Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Br+J+Clin+Pharmacol 2016 ; 82 (3): 673-82 Nephropedia Template TP {{tp|p=27135195|t=2016. Cell membranes? and how long drugs may exert beneficial pharmacological activity in vivo |pdf=|usr=}}{{27135195}} gab.com Text Cell membranes and how long drugs may exert beneficial pharmacological activity in vivo JO: Br J Clin Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=27135195 #FOAvip The time course of the beneficial pharmacological effect of a drug has long been considered to depend merely on the temporal fluctuation of its free concentration. Only in the last decade has it become widely accepted that target?binding kinetics can also affect in vivo pharmacological activity. Although current reviews still essentially focus on genuine dissociation rates, evidence is accumulating that additional micro?pharmacokinetic (PK) and ?pharmacodynamic (PD) mechanisms, in which the cell membrane plays a central role, may also increase the residence time of a drug on its target. The present review provides a compilation of otherwise widely dispersed information on this topic. The cell membrane can intervene in drug binding via the following three major mechanisms: (i) by acting as a sink/repository for the drug; (ii) by modulating the conformation of the drug and even by participating in the binding process; and (iii) by facilitating the approach (and rebinding) of the drug to the target. To highlight these mechanisms, we focus on drugs that are currently used in clinical therapy, such as the antihypertensive angiotensin II type 1 receptor antagonist candesartan, the atypical antipsychotic agent clozapine and the bronchodilator salmeterol. Although the role of cell membranes in PK?PD modelling is gaining increasing interest, many issues remain unresolved. It is likely that novel biophysical and computational approaches will provide improved insights in the near future. Twit Text FOAVip Cell membranes and how long drugs may exert beneficial pharmacological activity in vivo ????Br J Clin Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=27135195 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27135195 #FOAvip English Wikipedia <ref>{{Cite pmid|27135195}}</ref> Cell membranes? and how long drugs may exert beneficial pharmacological activity in vivo #MMPMID27135195 Vauquelin G Br J Clin Pharmacol 2016[Sep]; 82 (3): 673-82 PMID27135195show ga The time course of the beneficial pharmacological effect of a drug has long been considered to depend merely on the temporal fluctuation of its free concentration. Only in the last decade has it become widely accepted that target?binding kinetics can also affect in vivo pharmacological activity. Although current reviews still essentially focus on genuine dissociation rates, evidence is accumulating that additional micro?pharmacokinetic (PK) and ?pharmacodynamic (PD) mechanisms, in which the cell membrane plays a central role, may also increase the residence time of a drug on its target. The present review provides a compilation of otherwise widely dispersed information on this topic. The cell membrane can intervene in drug binding via the following three major mechanisms: (i) by acting as a sink/repository for the drug; (ii) by modulating the conformation of the drug and even by participating in the binding process; and (iii) by facilitating the approach (and rebinding) of the drug to the target. To highlight these mechanisms, we focus on drugs that are currently used in clinical therapy, such as the antihypertensive angiotensin II type 1 receptor antagonist candesartan, the atypical antipsychotic agent clozapine and the bronchodilator salmeterol. Although the role of cell membranes in PK?PD modelling is gaining increasing interest, many issues remain unresolved. It is likely that novel biophysical and computational approaches will provide improved insights in the near future. äCell membranes? and how long drugs may exert beneficial pharmacologica(epmc).pdf DeepDyve Pubget Overpricing