Matches in SemOpenAlex for { <https://semopenalex.org/work/W2346458802> ?p ?o ?g. }
- W2346458802 endingPage "682" @default.
- W2346458802 startingPage "673" @default.
- W2346458802 abstract "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." @default.
- W2346458802 created "2016-06-24" @default.
- W2346458802 creator A5065113357 @default.
- W2346458802 date "2016-05-29" @default.
- W2346458802 modified "2023-09-27" @default.
- W2346458802 title "Cell membranes… and how long drugs may exert beneficial pharmacological activity <i>in vivo</i>" @default.
- W2346458802 cites W1487006512 @default.
- W2346458802 cites W1496912321 @default.
- W2346458802 cites W1501203786 @default.
- W2346458802 cites W1501768464 @default.
- W2346458802 cites W1547158290 @default.
- W2346458802 cites W1564028741 @default.
- W2346458802 cites W1587498640 @default.
- W2346458802 cites W1661670649 @default.
- W2346458802 cites W1726768244 @default.
- W2346458802 cites W1772895962 @default.
- W2346458802 cites W1832201732 @default.
- W2346458802 cites W1911491421 @default.
- W2346458802 cites W1968620174 @default.
- W2346458802 cites W1970844675 @default.
- W2346458802 cites W1972292461 @default.
- W2346458802 cites W1974959226 @default.
- W2346458802 cites W1976969601 @default.
- W2346458802 cites W1979838968 @default.
- W2346458802 cites W1981332581 @default.
- W2346458802 cites W1986533233 @default.
- W2346458802 cites W1989035076 @default.
- W2346458802 cites W1993357003 @default.
- W2346458802 cites W1993575340 @default.
- W2346458802 cites W1998236781 @default.
- W2346458802 cites W1999225686 @default.
- W2346458802 cites W2003636671 @default.
- W2346458802 cites W2004364785 @default.
- W2346458802 cites W2006932016 @default.
- W2346458802 cites W2009139795 @default.
- W2346458802 cites W2010874272 @default.
- W2346458802 cites W2013143504 @default.
- W2346458802 cites W2013561183 @default.
- W2346458802 cites W2014718345 @default.
- W2346458802 cites W2015228718 @default.
- W2346458802 cites W2016408686 @default.
- W2346458802 cites W2020347831 @default.
- W2346458802 cites W2020622509 @default.
- W2346458802 cites W2020988821 @default.
- W2346458802 cites W2022551713 @default.
- W2346458802 cites W2023129450 @default.
- W2346458802 cites W2027521314 @default.
- W2346458802 cites W2029653823 @default.
- W2346458802 cites W2035164663 @default.
- W2346458802 cites W2037393447 @default.
- W2346458802 cites W2040973873 @default.
- W2346458802 cites W2041638206 @default.
- W2346458802 cites W2044309821 @default.
- W2346458802 cites W2048301351 @default.
- W2346458802 cites W2049617698 @default.
- W2346458802 cites W2051601355 @default.
- W2346458802 cites W2058698413 @default.
- W2346458802 cites W2062257232 @default.
- W2346458802 cites W2063424702 @default.
- W2346458802 cites W2063702932 @default.
- W2346458802 cites W2064914196 @default.
- W2346458802 cites W2066569368 @default.
- W2346458802 cites W2069104839 @default.
- W2346458802 cites W2070261427 @default.
- W2346458802 cites W2073874822 @default.
- W2346458802 cites W2074975964 @default.
- W2346458802 cites W2076472674 @default.
- W2346458802 cites W2079212311 @default.
- W2346458802 cites W2080894693 @default.
- W2346458802 cites W2083764503 @default.
- W2346458802 cites W2086836468 @default.
- W2346458802 cites W2088431582 @default.
- W2346458802 cites W2088519913 @default.
- W2346458802 cites W2088752137 @default.
- W2346458802 cites W2091768978 @default.
- W2346458802 cites W2093029369 @default.
- W2346458802 cites W2093727163 @default.
- W2346458802 cites W2095214288 @default.
- W2346458802 cites W2099576957 @default.
- W2346458802 cites W2101869072 @default.
- W2346458802 cites W2103948955 @default.
- W2346458802 cites W2106952947 @default.
- W2346458802 cites W2117003397 @default.
- W2346458802 cites W2123304597 @default.
- W2346458802 cites W2125446149 @default.
- W2346458802 cites W2126818937 @default.
- W2346458802 cites W2128191648 @default.
- W2346458802 cites W2139842115 @default.
- W2346458802 cites W2144663366 @default.
- W2346458802 cites W2152040050 @default.
- W2346458802 cites W2153308867 @default.
- W2346458802 cites W2155616119 @default.
- W2346458802 cites W2164633799 @default.
- W2346458802 cites W2167428574 @default.
- W2346458802 cites W2206592209 @default.
- W2346458802 cites W2331429966 @default.
- W2346458802 doi "https://doi.org/10.1111/bcp.12996" @default.
- W2346458802 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5338106" @default.