化療止吐藥 Aprepitant ( Emend ... - …

1 1 ( tsgh pharmacy newsletter ) 76 75 12 96 11 Aprepitant ( Emend ) (emesis) ( Chemotherapy induced nausea and vomiting, CINV ) ( acute CINV ) serotonin 24 ( delayed CINV ) substance P 24 ( anticipatory CINV ) CINV ( 90% ) ( 30% 90% ) ( 10% 30% ) ( < 10% )( ) Aprepitant ( Emend ) 2 70 - 80 5-HT3 receptor antagonist ( Granisetron Ondansetron )

2 Dexamethasone cisplatin 5- HT3 receptor antagonist substance P neurokinin ( NK1 ) receptor Aprepitant ( Emend ) 2005 NK1 receptor antagonist Aprepitant neurokinin 1 ( NK1 ) receptors serotonin ( 5- HT3 ) dopamine corticosteroid Aprepitant substance P neurokinin 1 ( NK1 ) receptors ( chemotherapy-induced nausea and vomiting, CINV ) ( postoperative nausea and vomiting, PONV ) Substance P tachykinin ( neurokinin ) Aprepitant neurokinin 1 ( NK1 ) receptors substance P Aprepitant neurokinin 1 ( NK1 ) receptors FDA 1.

3 2. 3. 3 (1) Aprepitant 125 mg PO 1 hr prior to chemotherapy 80 mg PO in the morning 80 mg PO in the morning 5- HT3 antagonist Ondansetron 32 mg IV 30 mins prior to chemotherapy Dexamethasone 12 mg PO 30 mins prior to chemotherapy 8 mg PO in the morning 8 mg PO in the morning 8 mg PO in the morning (2) Aprepitant 125 mg PO 1 hr prior to chemotherapy 80 mg PO in the morning 80 mg PO in the morning 5- HT3 antagonist Ondansetron (1)

4 8 mg PO 30 to 60 mins prior to chemotherapy (2) 8 mg PO 8 hours after the first dose Dexamethasone 12 mg PO 30 mins prior to chemotherapy (3) 40 mg Aprepitant ( 80 - 125mg ) 60 - 65% 3 - 4 95% 70 Cytochrome P450 CYP3A4 CYP1A2 CYP2C19 4 Aprepitant 9 -13 ALT AST Aprepitant B Aprepitant CYP3A4 ( inducer ) CYP2C9 Aprepitant pimozide terfenadine astemizole cisapride ( )

5 Aprepitant CYP3A4 (1) CYP3A4 ( CYP3A4 ) corticosteroid ( dexamethasone methylprednisolone ) ( etoposide vinorelbine docetaxel paclitaxel ifosfamide irinotecan ) benzodiazepines ( midazolam alprazolam triazolam ) fentanyl Aprepitant CYP3A4 Aprepitant CYP3A4 (2) CYP2C9 warfarin tolbutamine Aprepitant CYP2C9 warfarin Aprepitant 2 ( 7 10 ) prothrombin time (3) CYP3A4 azole ( ketoconazole itraconazole ) clarithromycin diltiazem nefazodone nelfinavir ritonavir Aprepitant CYP3A4.

6 CYP3A4 Aprepitant (4) CYP3A4 carbamazepine rifampin phenytoin CYP3A4 Aprepitant CYP3A4 ( phenytoin) (5) Aprepitant Aprepitant (6) Paroxetine Aprepitant AUC CMAX 5 Neurokinin-1 receptor antagonist 5- HT3 recepteor antagonist Aprepitant Granisetron Ondansetron Emend cap 80mg Kytril 1mg tab Kytril 1mg/ml inj Zofran 2mg/ml inj Antiemetic Substance P/ Neurokinin-1 Receptor antagonist Antiemetic 5-HT3 receptor antagonists Antiemetic 5- HT3 receptor antagonists 1.

7 2. 1. 2. 3. 4. 1. 2. 3. 60 - 65% 4 hrs ( Vd ) 70 L 95% CYP3A4 (major) CYP1A2(minor) CYP2C19(minor) 9 - 13 hrs Duration 24hrs ( Vd ) 2 - 4 L/kg 65% CYP3A N-demethylation oxidation followed by conjugation (11 - 12% unchanged, 48 - 49% as metabolites) (34 - 38% as metabolites ) 5 - 9 hrs Onset ~ 30 mins ( Vd ) - L/kg ( ) - L/kg ( ) 70~76% hydroxylation followed by glucuronide or sulfate conjugation demethylation(minor) (44 - 60%) ( 25% )

8 3 - hrs ( 18 - 22% ) ( 7 - 13% ) ( 9 - 12% ) ( 3 - 18% ) ( 11% ) ( 9 - 21% ) ( 3 - 18% ) ( 5 - 18% ) ( 9 - 27% ) / ( 9 - 13% ) ( 6 - 11% ) 6 Aprepitant Granisetron Ondansetron 1. Aprepitant 2. pimozide terfenadine astemizole cisapride granisetron 5- HT3 receptor antagonists ondansetron 5-HT3 receptor antagonists (*) 1. dexamethasone 5-HT3 2. 5- HT3 1.

9 2. / (1) Ondansetron 8 - 32mg Granisetron 1 - 3mg Tropisetron 5mg (2) Ondansetron 8 - 32mg Granisetron 1 - 3mg Tropisetron 5mg dexamethasone metoclopramide dexamethasone metoclopramide 3. ondansetron granisetron (1) total body or half body irradiation (2) pelvis or upper abdominal region of single irradiation dose> 6 Gy (3) dexamethasone metoclopramide rochlorperazine 1.

10 / ?/ B 2. ( 18 ) 3. Aprepitant CYP3A4 CYP2C9 1. / ?/ B 2. ( 2 ) 3. Granisetron 1. / ?/ B 2. ( 1 month) 3. Ondansetron 4. NT: $ 715 ( 80 mg TAB ) NT: $ 296 (TAB) NT: $ 450 (AMP) NT: $ 389 7 (*) ( ) 1. cisplatin ( > 50 mg/m2/day ) carmustine ( 250 mg/m2/day ) cyclophosphamide ( > 1500 mg/m2/day ) methotrexate ( gm/m2/day ) 2.