A commentary on the use of pharmacoenhancers in the pharmaceutical industry and the implication for DMPK drug discovery strategies
Xenobiotica(2022)
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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关键词
Pharmacoenhancer,ADMET,CYP inhibition,P-glycoprotein inhibition,pharmacokinetics
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