| Indication |
For the prevention of nausea and vomiting associated with highly
emetogenic cancer chemotherapy, including high-dose cisplatin (in
combination with other antiemetic agents). |
| Pharmacodynamics |
Aprepitant, an antiemetic, is 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). |
| 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. |
| Absorption |
The mean absolute oral bioavailability of aprepitant is approximately 60 to 65%. |
| Volume of distribution |
|
| Protein binding |
>95% |
| 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. |
| 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. |
| Half life |
9-13 hours |
| Clearance |
- Apparent plasma cl=62-90 mL/min
|
| Toxicity |
Not Available |
