Importance of Serum Concentration of Adefovir for Lamivudine-Adefovir Combination Therapy in Patients with Lamivudine-Resistant Chronic Hepatitis B
| Autor: | Hiroshi Aikata, Masao Shimizu, C. Nelson Hayes, Shosuke Kitamura, Daiki Miki, Kentaro Morimoto, Masataka Tsuge, Nobuhiko Hiraga, Hiromi Saneto, Michio Imamura, Fukiko Mitsui, Hiromi Abe, Harue Igarashi, Yoshiiku Kawakami, Tsuyoshi Hatakeyama, Takashi Kimura, Kazuaki Chayama, Tomokazu Kawaoka, Shoichi Takahashi |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Male Hepatitis B virus medicine.medical_specialty Combination therapy viruses Organophosphonates Cmax Biology medicine.disease_cause Antiviral Agents Gastroenterology Hepatitis B Chronic Internal medicine Drug Resistance Viral medicine Adefovir Humans Pharmacology (medical) Aged Pharmacology Reverse-transcriptase inhibitor Adenine virus diseases Lamivudine Middle Aged Hepatitis B medicine.disease digestive system diseases Treatment Outcome Infectious Diseases HBeAg DNA Viral Immunology Reverse Transcriptase Inhibitors Drug Therapy Combination Female medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 54:3205-3211 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.01372-09 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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