Fosaprepitant

Chemical properties

White Solid

The Uses of Fosaprepitant

Fosaprepitant is a selective neurokinin-1 (NK-1) receptor antahonist. Fosaprepitant is an antiemetic drug, a Aprepitant (A729800) prodrug.

The Uses of Fosaprepitant

An antiemetic drug, a Aprepitant prodrug.

The Uses of Fosaprepitant

Fosaprepitant is a selective neurokinin-1 (NK-1) receptor antagonist. Fosaprepitant is an antiemetic drug, a Aprepitant (A729800) prodrug.

Background

Fosaprepitant is an intravenously administered antiemetic drug. It is a prodrug of Aprepitant. It aids in the prevention of acute and delayed nausea and vomiting associated with chemotherapy treatment.

Indications

Fosaprepitant is indicated in adult and pediatric patients ≥6 months of age, in combination with other antiemetic agents, for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy, including high-dose cisplatin. It is also indicated for the treatment of delayed nausea and vomiting with initial and repeat courses of moderately emetogenic cancer chemotherapy.

What are the applications of Application

Fosaprepitant is a selective neurokinin-1 (NK-1) receptor antahonist

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].

Pharmacokinetics

Fosaprepitant is a prodrug of Aprepitant. Once biologically activated, the drug acts as a substance P/neurokinin 1 (NK1) receptor antagonist which, in combination with other antiemetic agents, is indicated for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy. Aprepitant is a selective high-affinity antagonist of human substance P/neurokinin 1 (NK1) receptors. Aprepitant has little or no affinity for serotonin (5-HT3), dopamine, and corticosteroid receptors, the targets of existing therapies for chemotherapy-induced nausea and vomiting (CI NV).

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

Aprepitant is metabolized primarily by CYP3A4 with minor metabolism by CYP1A2 and CYP2C19. Seven metabolites of aprepitant, which are only weakly active, have been identified in human plasma.

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.