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

ADMET P-glycoprotein inhibition CYP inhibition Pharmacoenhancer pharmacokinetics

Journal

Xenobiotica; the fate of foreign compounds in biological systems
ISSN: 1366-5928
Titre abrégé: Xenobiotica
Pays: England
ID NLM: 1306665

Informations de publication

Date de publication:
Aug 2022
Historique:
entrez: 20 12 2022
pubmed: 21 12 2022
medline: 22 12 2022
Statut: ppublish

Résumé

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.In order to overcome potentially suboptimal therapeutic exposures, nirmatrelvir is dosed in combination with ritonavir to boost the pharmacokinetics of the active product.Here we consider examples of drugs co-administered with pharmacoenhancers.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.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.

Identifiants

pubmed: 36537234
doi: 10.1080/00498254.2022.2130838
doi:

Substances chimiques

Myotonin-Protein Kinase EC 2.7.11.1
nirmatrelvir and ritonavir drug combination 0
Ritonavir O3J8G9O825

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

786-796

Auteurs

Vanessa Martins (V)

Astex Pharmaceuticals, Cambridge, UK.

Lynsey Fazal (L)

Astex Pharmaceuticals, Cambridge, UK.

Aram Oganesian (A)

Astex Pharmaceuticals, Pleasanton, CA, USA.

Alpesh Shah (A)

Astex Pharmaceuticals, Cambridge, UK.

Jessie Stow (J)

Astex Pharmaceuticals, Cambridge, UK.

Hugh Walton (H)

Astex Pharmaceuticals, Cambridge, UK.

Nicola Wilsher (N)

Astex Pharmaceuticals, Cambridge, UK.

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Classifications MeSH