Importance of Serum Concentration of Adefovir for Lamivudine-Adefovir Combination Therapy in Patients with Lamivudine-Resistant Chronic Hepatitis B

被引：5

作者：

Mitsui, Fukiko ^{[1
,3
]}

Tsuge, Masataka ^{[1
,2
,3
]}

Kimura, Takashi ^{[1
,3
]}

Kitamura, Shosuke ^{[1
,3
]}

Abe, Hiromi ^{[1
,3
]}

Saneto, Hiromi ^{[1
,3
]}

Kawaoka, Tomokazu ^{[1
,3
]}

Miki, Daiki ^{[1
,3
]}

Hatakeyama, Tsuyoshi ^{[1
,3
]}

Hiraga, Nobuhiko ^{[1
,3
]}

Imamura, Michio ^{[1
,3
]}

Kawakami, Yoshiiku ^{[1
,3
]}

Aikata, Hiroshi ^{[1
,3
]}

Takahashi, Shoichi ^{[1
,3
]}

Hayes, C. Nelson ^{[1
,3
]}

Igarashi, Harue ^{[4
]}

Morimoto, Kentaro ^{[4
]}

Shimizu, Masao ^{[4
]}

Chayama, Kazuaki ^{[1
,3
]}

机构：

[1] Hiroshima Univ, Grad Sch Biomed Sci, Dept Med & Mol Sci,Div Frontier Med Sci, Programs Biomed Res,Minami Ku, Hiroshima 7348551, Japan

[2] Hiroshima Univ, Nat Sci Ctr Basic Res & Dev, Hiroshima 7348551, Japan

[3] Hiroshima Univ, Liver Res Project Ctr, Hiroshima 7348551, Japan

[4] GlaxoSmithKline KK, Dev & Med Affairs Div, Bioanal Dept, Shibuya Ku, Tokyo 1518566, Japan

来源：

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY | 2010年 / 54卷 / 08期

关键词：

VIRUS POLYMERASE; HBV DNA; DIPIVOXIL; EMERGENCE; MUTATION; 9-(2-PHOSPHONYLMETHOXYETHYL)ADENINE; MECHANISMS; INFECTION; SELECTION; CIDOFOVIR;

D O I：

10.1128/AAC.01372-09

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Lamivudine (LMV)-adefovir pivoxil (ADV) combination therapy suppresses the replication of LMV-resistant hepatitis B virus (HBV), although its efficacy in suppressing HBV varies among patients. This study analyzed the clinical, virological, and pharmaceutical factors that influence the effect of the combination therapy. Patients negative for hepatitis B virus e antigen (HBeAg) and with low HBV DNA titers immediately prior to the combination therapy effectively cleared serum HBV DNA (P = 0.0348 and P = 0.0310, respectively). The maximum concentration of ADV in serum (ADV C-max) was higher in patients who showed HBV DNA clearance (P = 0.0392), and the cumulative clearance rates of HBV DNA were significantly higher in patients with ADV C-max equal to or greater than 24 ng/ml (P = 0.0284). HBeAg negativity and lower HBV DNA at the start of the combination therapy and higher ADV C-max were found to be independent factors for serum HBV DNA clearance. Serum creatinine increased significantly during the combination therapy, and the ADV C-max was higher in patients with low creatinine clearance rates. In conclusion, higher serum concentrations of ADV are associated with a good response to therapy based on clearance of HBV DNA in serum. However, care should be taken to prevent worsening of renal function due to high ADV serum concentrations.

引用

页码：3205 / 3211

页数：7

共 39 条

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