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DB06717 - Fosaprepitant


Identification
Name Fosaprepitant
Accession Number DB06717
Type small molecule
Description 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.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 614.4066
Groups approved
Monoisotopic Weight 614.116518403
Pharmacology
Indication For the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy.
Mechanism of action Aprepitant has been shown in animal models to inhibit emesis induced by cytotoxic chemotherapeutic agents, such as cisplatin, via central actions. Animal and human Positron Emission Tomography (PET) studies with Aprepitant have shown that it crosses the blood brain barrier and occupies brain NK1 receptors. Animal and human studies show that Aprepitant augments the antiemetic activity of the 5-HT3-receptor antagonist ondansetron and the corticosteroid ethasone and inhibits both the acute and delayed phases of cisplatin induced emesis. In summary, the active form of fosaprepitant is as an NK1 antagonist which is because it blocks signals given off by NK1 receptors. This therefore decreases the likelihood of vomiting in patients experiencing.
Absorption Not Available
Protein binding 95% +
Biotransformation 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.
Route of elimination Aprepitant is eliminated primarily by metabolism; aprepitant is not renally excreted. Aprepitant is excreted in the milk of rats. It is not known whether this drug is excreted in human milk.
Toxicity Not Available
Affected organisms Not Available
Interactions
Drug Interactions
Drug Mechanism of interaction
Corticotropin Fosaprepitant may increase the serum concentration of Corticosteroids (Systemic). The active metabolite aprepitant is likely responsible for this effect. The manufacturer of fosaprepitant states that oral dexamethasone doses should be reduced by 50% when coadministered with a fosaprepitant/aprepitant regimen to achieve dexamethasone concentrations similar to those achieved with dexamethasone alone.1 Dexamethasone doses used in clinical chemotherapy nausea/vomiting studies with aprepitant reflect this 50% decrease. Similarly, it is recommended that in order to achieve concentrations similar to those achieved with methylprednisolone alone, the intravenous methylprednisolone dose should be reduced by 25% and the oral methylprednisolone dose should be reduced by 50% when given together with a fosaprepitant/aprepitant regimen. Monitor for increased effects of systemic corticosteroids when coadmininistered with fosaprepitant or aprepitant.
Food Interactions Not Available

Predictions


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