Chemical Properties
White Solid
Uses
An antiemetic drug, a Aprepitant prodrug.
Uses
Fosaprepitant is a selective neurokinin-1 (NK-1) receptor antahonist. Fosaprepitant is an antiemetic drug, a Aprepitant (A729800) prodrug.
Definition
ChEBI: A morpholine derivative that is the (1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl ether of (3-{[(2R,3S)-3-(4-fluorophenyl)-2-hydroxymorpholin-4-yl]methyl}-5-oxo-4,5-dihydro-1H-1,2,4-triaz
l-1-yl)phosphonic acid.
Biological Activity
fosaprepitant (l-758,298 mk-0517) is an antagonist of neurokinin-1[1].fosaprepitant has shown the pharmacodynamic function by its active metabolite aprepitant. fosaprepitanot has been found to be a highly selective antagonist of the nk-1 receptor and inhibit the cation of substance p. in addition, fosaprepitant has been exhibited to have the effect on cisplatin induced emesis in the classical ferret model. besides, because of the brain penetrating of aprepitant, fosaprepitant has been revealed to have a very high affinity for the nk-1 receptor and increase the efficacy by dexamethasone, granisetron and so on. fosaprepitant has been evaluated to use in the prevention of chemotherapy-induced nausea and vomiting (cinv) by combination with a 5-ht3 antagonist and a steroid [1].
Drug interactions
Potentially hazardous interactions with other drugs
Antidepressants: avoid with St John’s wort.
Antipsychotics: avoid with pimozide.
Cytotoxics: possibly increases bosutinib
concentration - avoid or reduce bosutinib dose.
Oestrogens and progestogens: may cause
contraceptive failure.
Metabolism
Fosaprepitant is a prodrug and is rapidly metabolised
to aprepitant. Aprepitant undergoes extensive hepatic
metabolism, mainly via oxidation by the cytochrome
P450 isoenzyme CYP3A4; the isoenzymes CYP1A2
and CYP2C19 mediate minor metabolic pathways. The
resultant metabolites have weak activity and are excreted
in the urine and in the faeces.
References
[1] van belle sj1, cocquyt v. fosaprepitant dimeglumine (mk-0517 or l-785,298), an intravenous neurokinin-1 antagonist for the prevention of chemotherapy induced nausea and vomiting.expert opin pharmacother. 2008 dec; 9(18):3261-70.
