Fosaprepitant

Fosaprepitant (L-758298) is a neurokinin-1 receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting.IC50 Value:Target: NK1 receptorin vitro: Fosaprepitant (also known as MK-0517 and L-758,298) is a water-soluble phosphoryl prodrug for aprepitant, which, when administered intravenously, is converted to aprepitant within 30 min of intravenous administration via the action of ubiquitous phosphatases. Owing to the rapid conversion offosaprepitant to the active form (aprepitant), fosaprepitant 115 mg provided the same aprepitant exposure in terms of AUC as aprepitant 12 mg orally, and fosaprepitant is expected to provide a correspondingly similar antiemetic effect as aprepitant [1]. in vivo: Fosaprepitant is well tolerated with mild to moderate venous irritation being the only additional toxicity to those seen with oral aprepitant, and that is a function of dose, concentration, and infusion rate [2]. Patients receiving cisplatin ≥ 70 mg/m(2) for the first time received ondansetron and dexamethasone with a standard aprepitant regimen (125 mg on day 1, 80 mg on day 2, 80 mg on day 3) or a single-dose fosaprepitant regimen (150 mg on day 1) [3]. Single-dose fosaprepitant used in combination with granisetron and dexamethasone was well-tolerated and effective in preventing chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic cancer chemotherapy, including high-dose cisplatin [4].

Signaling Pathways >> GPCR/G Protein >> Neurokinin Receptor

Signaling Pathways >> Neuronal Signaling >> Neurokinin Receptor

Research Areas >> Neurological Disease

[1]. Navari RM. Fosaprepitant: a neurokinin-1 receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting. Expert Rev Anticancer Ther. 2008 Nov;8(11):1733-42.

[2]. Olver IN. Prevention of chemotherapy-induced nausea and vomiting: focus on fosaprepitant. Ther Clin Risk Manag. 2008 Apr;4(2):501-6.

[3]. Grunberg S, et al. Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with cisplatin therapy: randomized, double-blind study protocol--EASE. J Clin Oncol. 2011 Apr 10;29(11):1495-501.

[4]. Saito H, et al. Efficacy and safety of single-dose fosaprepitant in the prevention of chemotherapy-induced nausea and vomiting in patients receiving high-dose cisplatin: a multicentre, randomised, double-blind, placebo-controlled phase 3 trial. Ann Oncol.

Substance P acetate salt | rolapitant | SB-222200 | Fezolinetant | Netupitant | [Sar9,Met(O2)11]-Substance P TFA | MLE-4901 | Succinyl-(Asp6,N-Me-Phe8)-Substance P (6-11) | Maropitant | NKP608 | Serlopitant | Talnetant | Y1 receptor antagonist 1 | [bAla8]-Neurokinin A(4-10)