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- W4309378620 endingPage "2493" @default.
- W4309378620 startingPage "2493" @default.
- W4309378620 abstract "(1) Background: Oral targeted anticancer drugs are victims of presystemic pharmacokinetic drug−drug interactions (DDI). Identification of the nature of these DDIs, i.e., enzyme-based or/and transporter-based, is challenging, since most of these drugs are substrates of intestinal and/or hepatic cytochrome P-450 enzymes and of intestinal membrane transporters. (2) Methods: Variations in mean absorption time (MAT) between DDIs and control period (MAT ratios < 0.77 or >1.30) have been proposed to implicate transporters in DDIs at the intestinal level. This methodology has been applied to a large set of oral targeted anticancer drugs (n = 54, involved in 77 DDI studies), from DDI studies available either in the international literature and/or in publicly accessible FDA files. (3) Results: Significant variations in MAT were evidenced in 33 DDI studies, 12 of which could be explained by modulation of an efflux transporter. In 21 DDI studies, modulation of efflux transporters could not explain the MAT variation, suggesting a possible relevant role of influx transporters in the intestinal absorption. (4) Conclusions: This methodology allows one to suggest the involvement of intestinal transporters in DDIs, and should be used in conjunction with in vitro methodologies to help understanding the origin of DDIs." @default.
- W4309378620 created "2022-11-26" @default.
- W4309378620 creator A5018374160 @default.
- W4309378620 creator A5064627425 @default.
- W4309378620 creator A5084743277 @default.
- W4309378620 date "2022-11-17" @default.
- W4309378620 modified "2023-09-26" @default.
- W4309378620 title "Involvement of Transporters in Intestinal Drug–Drug Interactions of Oral Targeted Anticancer Drugs Assessed by Changes in Drug Absorption Time" @default.
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