Therapeutics of Clinical Drugs 臨床藥物治療學 Thymalfasin 用於治療 C 型肝炎 光田綜合醫院藥劑部藥師白雅君 賴建名 摘要 C C interferon ribavirin Thymalfasin C phase III thymalfasin C C thymosin α1 thymalfasin 壹 前言 C interferon ribavirin interferon ribavirin Thymalfasin (thymosin α1, Zadaxin) C B C phase III interferon ribavirin C 1 thymalfasin C 貳 C 型肝炎診斷 C C 2 C (polymerase chain reaction, PCR) C (hepatitis C virus ribonucleic acid, HCV RNA) PCR PCR C C Child- Turcotte-Pugh Scoring System METAVIR Scoring System 1 藥學雜誌第 112 冊 51
臨床藥物治療學 Therapeutics of Clinical Drugs 參 C 型肝炎治療目標 (American Association for the Study of Liver Disease, AASLD) C (sustained virologic response, SVR) C SVR (alanine aminotransferase, ALT) HCV RNA 1 肆 C 型肝炎藥品治療 C 1 7 2 C (genotype) 6 50 1 1a 1b 3 FDA C interferon ribavirin4 12 24 HCV RNA HCV RNA HCV RNA 100-1000 RNA copies/ml (early virologic response, EVR) 12 HCV RNA HCV RNA 2-log10 SVR 4 genotype 2 genotype 3 2448 ( 5,6,7 ) 表一病毒基因型不同建議的藥品療程 Genotype 1 Genotype 2 & Genotype 3 Genotype 4 <65kg: 800 mg/day Ribavirin: 800 mg/day Ribavirin: 800 mg/day <65kg: 800 mg/day 24 * *Peginterferon alfa-2b: 1.5 μg/kg (24HCV RNA 24 HCV RNA ) 52 THE JOURNAL OF TAIWAN PHARMACY Vol.28 No.3
Thymalfasin C 伍 Thymalfasin 臨床應用一 藥物性質 (thymus) Thymalfasin thymosin α128 ()3108 daltons1.6 mg thymosin α1 50 mg mannitol sodium phosphate ph 6.8 1.5 2.4 8 圖一 Thymalfasin 主要的 28 個胺基酸二 適應症 Thymalfasin C thymalfasin C interferon interferon ribavirin thymalfasin thymalfasin thymalfasin () 9 表二核准上市國家及臨床試驗項目 C (Chronic hepatitis C) Phase III B (Chronic hepatitis B) (Vaccine Adjuvant) (Immunostimulant) (Cancer Adjuvant) 三 藥品療程 interferon ribavirin thymalfasin 1.6 mg 24 HCV RNA C 72 1 四 副作用 Phase II (Malignant Melanoma) Phase II (Liver Cancer) Thymalfasin 藥學雜誌第 112 冊 53
臨床藥物治療學 Therapeutics of Clinical Drugs interferon ribavirin () 1,5,8 表三合併療法藥品副作用 thymalfasin interferon ribavirin 750/mm 3 500/mm 3 i n t e r- feron 10 g/dl ( ) 8.5 g/ dl 五 作用機轉 TSH Thymalfasin thymalfasin (Natural killer cell) T CD 8 (Cluster of Differentiation 8 receptors)t CD4 (Cluster of Differentiation 4 receptors) thymalfasin MHC (major histocompatibility complex) class Ι MHC class Ι T CD8 () 9 圖二 Thymalfasin 作用機轉陸 C 型肝炎新合併療法相關研究 2009 552 peginterferon alfa-2a peginterferon alfa-2b ribavirin genotype 1 87.6% peginterferon alfa-2a ribavirin thymalfasin 275 peginterferon alfa-2a ribavirin 277 SVR 94% 87.9%48 72 24 41% HCV RNA 26.3% (p=0.048) 10 20082004 interferon ribavirin thymalfasin (1.6 mg2 ) peginterferon alfa- 2a (180 μg ) ribavirin (800-1200 mg/ ) 1224 PCR 2008 24 21.1% SVR genotype 1 23.5% 54 THE JOURNAL OF TAIWAN PHARMACY Vol.28 No.3
Thymalfasin C thymalfasin thymalfasin 1,11 柒 結論 thymalfasin C p h a s e III197970 thymalfasin C thymalfasin thymalfasin C 參考資料 : 1. Poo JL, Sánchez Avila F, Kershenobich D, et al: Efficacy of triple therapy with thymalfasin, peginterferon -2a, and ribavirin for the treatment of hispanic chronic HCV nonresponders. Annals of Hepatology 2008; 7(4): October-December: 369-375. 2. Rustgi V: Combination therapy of thymalfasin (thymosin-alpha 1) and peginterferon alfa-2a in patients with chronic hepatitis C virus infection who are non-responders to standard treatment. Journal of Gastroenterology and Hepatology (2004) 19, S76-S78. 3. - C Available from: http://www.cdc.gov. tw/. Accessed August 20, 2009, 2008. 4. Dienstag JL, McHutchison JG: American Gastroenterological Association medical position statement on the management of hepatitis C. Gastroenterology 2006Jan; 130(1): 225-30. 5. PEG-INTRON 6. Pagsys 7. Rebetol 8. Zadaxin 9. SciClone Pharmaceuticals. Product Development. Available from: http://www.sciclone.com/product/zadaxin.php. Accessed August 28, 2009, 2009. 10. Ciancio A, Andreone P, Kaiser S, et al: Thymosin alfa-1 in association with Peg-IFN alfa-2a and Ribavirin(RBV) for retreatment of chronic hepatitis C (CHC) patients non-responders to Peg-IFNs and RBV. AASLD 2009 Abstracts. 11. Poo JL, Sánchez Avila F, Kershenobich D, et al: Triple combination of thymalfasin, peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior interferon and ribavirin treatment: 24-week interim results of a pilot study. Journal of Gastroenterology and Hepatology (2004) 19, S79-S81. Thymalfasin for Treating Hepatitis C Ya-Chun Pai, Jian-Ming Lai Kuang Tien General Hospital Abstract Hepatitis C accounts for a sizable proportion of cases of chronic liver disease, liver disease deaths, and cases of hepatocellular carcinoma and represents the most common indication for liver transplantation. The majority of patients who are infected with genotype 1 HCV and have high viral loads do not achieve a sustained response. Thymalfasin (Zadaxin, TA-1, thymosin alpha 1) is in phase III trials for the treatment of hepatitis C virus (HCV) in patients who are non-responders to prior therapy. Thymalfasin showed efficacy in the treatment of chronic HCV infection and demonstrated a consistent pattern of tolerability and safety in clinical trials. Use of immunomodulators such as thymalfasin may have an adjuvant role in promoting responses for both current and future hepatitis C treatment modalities. 藥學雜誌第 112 冊 55