Mefenamic Acid 導致罕見的肝細胞混合膽汁鬱積性 肝炎及史 …

1 2010 21 66-71 710 901 Mefenamic acid 1 2 3 4 2 5 5 1 1 2 3 4 5 nonsteroidal anti-infl-ammatory drugs NSAIDs Mefenamic acid fenamates NSAIDs1 25 1 5% 1 (Stevens-Johnson Syndrome SJS) Mefenamic acid SJS 2,3 42 Mefenamic acid SJS 42 aminotransferase nonsteroidal anti-inflammatory drugs NSAIDs fenamates NSAIDs Mefenamic acid (Stevens-Johnson Syndrome SJS)

2 NSAIDs drug-induced liver injury DILI SJS NSAIDs Mefenamic acid SJS NSAIDs DILI SJS pharmacogenomics (Drug-induced liver injury) (Cholestatic hepatitis) (Stevens-Johnson syndrome) Mefenamic acid Mefenamic acid 250 mg aluminum hydroxide 324 mg C, 109/68 mmHg 70 20 (corneal ersion) (yellowish discolorization ) ( shifting dullness) X 103 cells/ L(Reference Range RR 3400-9100 cells/ L) %(RR 0-4 %) g/dL(RR g/dL)

3 X 105 platelets/ L(RR X 105 platelets/ L) 8 mg/dL(RR 6-22 mg/dL) mg/dL(RR mg/dL) (alanine aminotransferase, ALT), 627 IU/L(RR 10-50 IU/L) (aspartate aminotransferase, AST), 464 IU/L(RR 10-50 IU/L); mg/dL(RR mg/dL) ( ALT AST ) mg/dL(RR mg/dL) (alkaline phosphatase, AP), 455 IU/L(RR 66-220 IU/ L) - (gamma-glutamyl transpeptidase rGT), IU/L(RR 4-63 IU/L) g/dL( g/dL) prothrombin time(PT), ( ) PT control, PT INR, anti-HAV IgM, HBs Ag, anti-HBc IgM anti-HCV IgG (herpes simplex virus)

4 Type1 type 2 IgM cytomegalovirus IgM Epstein-Barr virus IgM SJS SJS NSAIDs hydrocortisone 100 mg 20 prednisolone 30 (a) (b) ALT AST Bil-T ALT level, AST level (IU/L)monthASTALTBil-TBil-T(mg/dL)67 Mefenamic acid mg/ 57 (ALT, 916 IU/L; AST, 287 IU/ L; mg/dL, ) prednisolone ( 30 mg 40 mg) ursodeoxycholic acid (UDCA) 600 mg 59 (zone 3) 75 ALT, 486 IU/ L; AST, 119 IU/ L; mg/dL PT anti-HCV IgG prednisolone 90 105 mg/dL, 260 ALT, 49 IU/ L.

5 AST, 39 IU/ L, Mefenamic acid Mefenamic acid SJS 2,3 SJS Mefenamic acid SJS A, B, C type1 type 2 IgM IgM Epstein-Barr virus IgM Navarro 4 SJS Mefenamic acid rGT AP 5 SJS 6 AP H E (a).

6 (40x) P C (b). (zone 3) (200 x) (c). (400 x, ) 68 rGT SJS 7 (drug-induced liver injury DILI)8 DILI " " " " " " 9 10 R 9 R 627 50 / 455 220 = R 5 DILI DILI 11 DILI 9 Tolman NSAIDs DILI 1%12 Lanza 68,028 NSAIDs 37/100,000 NSAIDs 51/100.

7 000 13 NSAIDs DILI Aspirin diclofenac sulindac 14 Aspirin " " Bjorkman Aspirin 14 Diclofenac " idiosyncratic metabolic toxicity " 15 14,15 Aithal 44 DILI 50 NSAIDs NSAIDs diclofenac 16 Sulindac " idiosyncratic immunologic toxicity " 17 14 " " Steenbergen NSAIDs 17 ( adduct) 18 19 ( )

8 19 3 DILI 8 1 5 17 7 Mefenamic acid 20 tight junctions 20 8 SJS 21 1-5%21 7-21 21 SJS ( allopurinol) (sulfonamides ) (carbamazepine phenytoin ) 69 Mefenamic acid NSAIDs piroxicam, sulindac, diclofenic 21 SJS 10% 8% 10% 30% SJS toxic epidermal necrolysis TEN 30% TEN21 10% 21 UDCA 8,22 SJS SJS 3,23 UDCA 8 DILI SJS 21.

9 24 SJS TEN 2 gm25 DILI SJS Aithal DILI 16 SJS 20 ALT ( ) Mefenamic acid UDCA SJS (Major Histocompatibility Complex MHC)class I 26,27 Human Leukocyte Antigens HLA T 26-28 HLA-B ( HLA-B 1502 carbamazepine-SJS HLA-B 5801 allopurinol-SJS)26-28 28 HLA 26-28 Mefenamic acid SJS 1.

10 Burke A, Smyth EM, FitzGerald GA. Analgesic-antipyretic and antiinflammatory agents; pharmacotherapy of gout. In: Brunton LL, eds. Goodman & Gilman's the Pharmacological Basis of Therapeutics. 11th ed. New York: McGraw-Hill 2006; 697. 2. Chan JCN, Lai FM, Critchley AJHJ. A case of Stevens-Johnson syndrome, cholestatic hepatitis and haemolytic anaemia associated with use of Mefenamic acid . Drug Safety 1991; 6: 230-4. 3. Morelli MS, O'brien FX. Stevens-Johnson syndrome and cholestatic hepatitis. Dig Dis Sci 2001; 46: 2385-8. 4. Navarro VJ, Senior JR. Drug-related hepatotoxicity.