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1、84 Notes Saudi Pharmaceutical Journal, Vol. 14, No. 1 January 2006 APREPITANT: A PROMISING ANTIEMETIC FOR PREVENTION OF CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING Mohammed A. Aseeri Most patients who undergo chemotherapy have noted that nausea and vomiting are the most feared and distressing side-effe
2、cts of cancer treatment (1). Nausea and vomiting from chemotherapy can be classified as acute, delayed, or anticipatory. Acute emesis generally occurs within 24 hours of chemotherapy administration; while delayed nausea and vomiting begin 24 hours after chemotherapy and may continue for up to one we
3、ek. Anticipatory emesis occurs prior to chemotherapy in patients who anticipate another episode by sight, odors, or memory of the place where acute nausea and vomiting occurred (2,3). Different neurotransmitters found in the gastrointestinal tract (GIT) and central nervous system (CNS) mediate the p
4、athophysiology of chemotherapy-induced nausea and vomiting (CINV).These include dopamine, histamine, acetylcholine, serotonin, and substance P; which act directly and indirectly on the vomiting center located in the lateral reticular formation of the medulla (1,4). Substance P is a member of the tac
5、hykinins family of neuropeptides.The biological activity of this substance is to induce vomiting mediated by neurokinin-1 (NK1) receptors located primarily in the GIT and the CNS (5). Both NK1 receptors and substance P play a significant role in the pathogenesis of acute and delayed CINV. Introducti
6、on The American Society of Clinical Oncology (ASCO) guidelines suggest that the potential effect of CINV is influenced by the emetogenicity level of the chemotherapeutic agent and patient character- istics. Coadministration of chemothera-peutic agents and repeated cycles of chemotherapy increase the
7、 risk of CINV. Furthermore, patient characteristics can increase the risk for CINV; adults under 50 years old, female patients, children, and those with a history of motion sickness are more likely to have CINV (6, 7). Currently an antagonist of 5-hydroxy- tryptamine 3 receptors (5-HT3) (e.g. ondans
8、etron) in combination with oral dexametha-sone is used to control acute emesis after highly emetogenic chemotherapy (3). However, the 5-HT3 antagonists do not show efficacy against delayed emesis. Although the effectiveness of the current antiemetic agents has controlled and decreased the incidence
9、. . emesis . . . ( substance P) . ( NK1) . Department of Pharmacy Practice, North Dakota State University 123D Sudro Hall, Fargo, North Dakota 58105, USA E-mail: Mohammed.Aseerindsu.edu APREPITANT 85 Saudi Pharmaceutical Journal, Vol. 14, No. 1 January 2006 and severity of CINV, nausea and vomiting
10、continue to occur on a regular basis. The pathophysiology of delayed emesis is still not completely understood and difficult to control. It has been estimated that up to 80% of patients receiving cisplation at doses of 50 mg/m or higher experience delayed nausea and vomiting despite good control of
11、acute emesis.3 Hence, newer antiemetic agents that can control delayed emesis are needed. Aprepitant (Emend, Merck and Co Inc) is an antagonist of substance P that blocks NK-1 receptors. This drug was approved by the Food and Drug Administration (FDA) in April, 2003, for the prevention of acute and
12、delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy, including high- dose cisplatin (8). It represents a new class of antiemetics, the NK-1 receptor antagonists. Aprepitant in combination with other antiemetics such as 5-HT3 antagonists and oral dexamethasone has demonstrated efficacy in the control of both acute
