A commentary on the use of pharmacoenhancers in the pharmaceutical industry and the implication for DMPK drug discovery strategies

被引:1
|
作者
Martins, Vanessa [1 ,3 ]
Fazal, Lynsey [1 ]
Oganesian, Aram [2 ]
Shah, Alpesh [1 ]
Stow, Jessie [1 ]
Walton, Hugh [1 ]
Wilsher, Nicola [1 ]
机构
[1] Astex Pharmaceut, Cambridge, England
[2] Astex Pharmaceut, Pleasanton, CA USA
[3] Astex Pharmaceut, 436 Cambridge Sci Pk, Cambridge CB40QA, England
关键词
Pharmacoenhancer; ADMET; CYP inhibition; P-glycoprotein inhibition; pharmacokinetics; P-GLYCOPROTEIN INHIBITOR; PLASMA-PROTEIN BINDING; IN-VITRO; ORAL BIOAVAILABILITY; CYTOCHROME-P450; INHIBITION; SELECTIVE INHIBITOR; FATTY-ACIDS; POTENT; RITONAVIR; PHARMACOKINETICS;
D O I
10.1080/00498254.2022.2130838
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1. Paxlovid, a drug combining nirmatrelvir and ritonavir, was designed for the treatment of COVID-19 and its rapid development has led to emergency use approval by the FDA to reduce the impact of COVID-19 infection on patients. 2. In order to overcome potentially suboptimal therapeutic exposures, nirmatrelvir is dosed in combination with ritonavir to boost the pharmacokinetics of the active product. 3. Here we consider examples of drugs co-administered with pharmacoenhancers. 4. Pharmacoenhancers have been adopted for multiple purposes such as ensuring therapeutic exposure of the active product, reducing formation of toxic metabolites, changing the route of administration, and increasing the cost-effectiveness of a therapy. 5. We weigh the benefits and risks of this approach, examining the impact of technology developments on drug design and how enhanced integration between cross-discipline teams can improve the outcome of drug discovery.
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页码:786 / 796
页数:11
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