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- W2330486650 abstract "P-glycoprotein (P-gp), an efflux transporter expressed in tumour and normal tissues, may significantly affect pharmacodynamics and pharmacokinetics of the drug, compromising its pharmacological effect. During drug discovery and development (DDD) programs, identification of compounds that are substrates, inhibitors or inducers of P-gp can aid drug candidate selection and optimization and eventually develop drugs with ideal pharmacological profiles and low potential for drug-drug interactions mediated by P-gp. Toward this end, rhodamine 123 (Rho 123), digoxin and talinolol are commonly used as P-gp substrates probes in several in vitro and in vivo models. This article summarized the significant role of P-gp in drug disposition and the impact of its modulation in the current DDD. Furthermore, an overview of several examples from literature where Rho 123, digoxin and talinolol were used as P-gp substrate probes during different stages of DDD was also herein described. While Rho 123 seemed to be successfully used in early drug discovery and non-clinical development stages, digoxin and talinolol are more frequently applied as clinical in vivo probe drugs for P-gp. However for regulatory submission, Rho 123 cannot be used neither in in vitro investigations and therefore digoxin is preferred since its advantages over talinolol." @default.
- W2330486650 created "2016-06-24" @default.
- W2330486650 creator A5005703800 @default.
- W2330486650 creator A5019069584 @default.
- W2330486650 creator A5031340729 @default.
- W2330486650 date "2011-01-01" @default.
- W2330486650 modified "2023-10-18" @default.
- W2330486650 title "In vitro and In vivo Relevance of the P-glycoprotein Probe Substrates in Drug Discovery and Development: Focus on Rhodamine 123, Digoxin and Talinolol" @default.
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