• 한국임상약학회지
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• 제23권2호
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• pp.175-177
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• 2013

Lamivudine and adefovir are medications used to treat hepatitis B. We observed the occurrence of tinnitus after administering lamivudine and adefovir to a 49-year-old hepatitis B patient for two months. The patient had no comorbidities and no history of ear diseases, including tinnitus, and was not taking any other medications. In general, neither lamivudine nor adefovir are known to induce tinnitus as an adverse reaction. A literature search revealed that this is the first case in which tinnitus occurred after lamivudine and adefovir were administered to a hepatitis B patient. Therefore, we believe that this case is clinically valuable and decided to report it.

• Asian Pacific Journal of Cancer Prevention
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• 제13권11호
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• pp.5463-5467
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• 2012

Hepatitis B virus (HBV) infection is contagious with transmissiobn vertically or horizontally by blood products and body secretions. Over 50% of Iranian carriers contracted the infection prenatally, making this the most likely route of transmission of HBV in Iran. To evaluate the resistance to adefovir (ADV) therapy in patients with chronic hepatitis B infection, a study was conducted on 70 patients (63 males and 7 females), who had received in first line lamivudine and second line adefovir. All were tested for the presence of hepatitis B surface antigen (HBsAg), hepatitis B envelope antigen (HBeAg), serum alanine amino transferase (ALT) level and HBV DNA load before and after treatment with ADV. In all samples, resistance to lamivudine and ADV was tested with real time PCR. Among seventy patients with chronic hepatitis B infection, 18 (25.7%) were resistant to LAM and 8 (11.4%) were resistant to ADV. Only one patient was negative for the presence of HBS-Ag (5.6%) and two were negative for HBe-Ag (11.1%). In this study we used a new method (ALLGIO probe assay) that has high sensitivity in detection of adefovir resistance mutants, which we recommend to other researchers. Mutant strains of the YMDD motif of HBV polymerase can be found in some patients under treatment with lamivudine and ADV. ADV has been demonstrated to be efficient in patients with lamivudine resistant HBV.

• 약학회지
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• 제54권4호
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• pp.316-321
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• 2010

Adefovir dipivoxil which was originally developed by Gilead Sciences has been used as treatments of HIV and HBV, especially a therapeutics for HBeAg positive and negative chronic patients. We developed highly efficient purification method using reverse phase column chromatography for mass production and a stable amorphous Adefovir dipivoxil using solid dispersion method. Reverse phase column chromatography led to highly pure product, more than 99.7% by HPLC and can be used for mass production compared with normal column chromatography. Solid dispersion method containing watersoluble polymer and Isomalt showed improved stability of amorphous Adefovir dipivoxil against heat and moisture.

• 한국임상약학회지
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• 제22권1호
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• pp.81-86
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• 2012

This study was aimed to examine the prescribing patterns of antivirals in outpatients with chronic hepatitis B (CHB), using National Health Insurance adjudicated claims data (total 1,426,065 claims) dated March 19, 2008 submitted from nationwide healthcare providers to Health Insurance Review and Assessment Service. From the data, there were 2,965 claims with CHB diagnosis (ICD-10 code B18.0 and B18.1), and 44.2% (1,311 claims) of the CHB related claims included antivirals such as lamivudine, clevudine, adefovir and entecavir. Lamivudine, adefovir, clevudine and entecavir shared 54.9%, 19.9%, 13.2% and 11.9%, respectively, among antiviral prescriptions. Adefovir and entecavir 1mg presumed as the 2nd line therapy for HBV resistant cases were shared 23.3% of overall antiviral prescriptions. There were statistically significant difference in prescription patterns according to age and institution type: Lamivudine usage was higher in younger (< 20 years old) and older age group (> 70 years old) than the others (p = 0.016), and adefovir and entecavir, which were relatively newer antivirals, had higher prescription rates in higher level of institutions such as tertiary hospitals than the others (p < 0.001). This study would be of help to make an appropriate drug therapy plan for patients with CHB.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5489-5494
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• 2013

In the current study we aimed to show the common YMDD motif mutations in viral polymerase gene in chronic hepatitis B patients during lamivudine and adefovir therapy. Forty-one serum samples obtained from chronic hepatitis B patients (24 male, 17 female; age range: 34-68 years) were included in the study. HBV-DNA was extracted from the peripheral blood of the patients using an extraction kit (Invisorb, Instant Spin DNA/RNA Virus Mini Kit, Germany). A line probe assay and direct sequencing analyses (INNO-LIPA HBV DR v2; INNOGENETICS N.V, Ghent, Belgium) were applied to determine target mutations of the viral polymerase gene in positive HBV-DNA samples. A total of 41 mutations located in 21 different codons were detected in the current results. In 17 (41.5%) patients various point mutations were detected leading to lamivudin, adefovir and/or combined drug resistance. Wild polymerase gene profiles were detected in 24 (58.5%) HBV positive patients of the current cohort. Eight of the 17 samples (19.5%) having rtM204V/I/A missense transition and/or transversion point mutations and resistance to lamivudin. Six of the the mutated samples (14.6%) having rtL180M missense transversion mutation and resistance to combined adefovir and lamivudin. Three of the mutated samples (7.5%) having rtG215H by the double base substituation and resistance to adefovir. Three of the mutated samples (7.5%) having codon rtL181W due to the missense transversion point mutations and showed resistance to combined adefovir and lamivudin. Unreported novel point mutations were detected in the different codons of polymerase gene region in the current HBV positive cohort fromTurkish population. The current results provide evidence that rtL180M and rtM204V/I/A mutations of HBV-DNA may be associated with a poor antiviral response and HBV chronicity during conventional therapy in Turkish patients.

• 폴리머
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• 제37권5호
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• pp.663-668
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• 2013

고분자가 adefovir dipivoxil(AD)과 suberic acid(SUB)의 공결정 형성에 미치는 영향을 연구하였다. 고분자 첨가제는 poly(ethylene glycol)(PEG)과 poly(acrylic acid)(PAA)를 이용하였다. 용액에서 AD와 SUB를 혼합한 후에 고분자를 첨가하여 공결정을 제조했을 때는, 고분자의 영향은 결정모양과 결정성을 일부 변화시키는 것에 한정되었는데, 이러한 영향은 고분자 없이도 용액에 과량의 SUB를 이용하거나 용매첨가 분쇄법으로 유도할 수 있었다. 한편, 용액에서 AD와 고분자를 혼합한 후에 SUB를 첨가하여 공결정을 제조했을 때는, PEG의 경우 공결정의 변화를 훨씬 효과적으로 유도하였는데 결정성을 기준으로 같은 농도에서 3배 이상의 효과를 보였다. 또한 PAA의 경우에는 결정의 형성을 완전히 억제하는 효과를 보였다. 본 연구의 결과는 공결정 형성에 미치는 고분자의 영향을 단순히 혼합순서를 바꾸어서 조율할 수 있는 예를 보여 주었다.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제11권2호
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• pp.143-149
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• 2008

목 적: 라미부딘 내성을 가진 소아 청소년 만성 B형 간염 환자들에게 아데포비어로 치료 시작 후 그 치료효과를 평가하고 장기 치료의 안정성에 대해 검증하고자 하였다. 방 법: 경북대학교병원 소아청소년과 및 소화기내과에서 라미부딘 내성 만성 B형 간염으로 진단된 환아 16명(남아 12명, 여아 4명, 4.3~20.9세, 평균 14.2세)을 대상으로 2004년 3월 이후 아데포비어 치료를 시작하여 2008년 4월까지 평균 27개월(9~49개월)동안 추적 관찰하면서 연구를 진행하였다. 치료에 대한 효과는 치료 시작 후 혈청 ALT치의 정상화와 HBV DNA의 음전 및 HBeAg/anti-HBe로의 혈청전환을 모두 만족할 때 치료반응이 있다고 정의하였다. Kplan-Meier법을 이용한 누적 ALT 정상화율, HBV DNA 음전율(<357 IU/mL), HBeAg titer 2 $log_{10}$ IU/mL 감소율, HBeAg 소실율, HBeAg 혈청전환율을 치료 시작 12, 24, 36, 48개월에서 구하였다. 결 과: 아데포비어로 치료 시작 후 치료 반응은 16명 중 3명(18.8%)에서 보였고 Kaplan-Meier법에 의한 누적 ALT치 정상화율은 치료 시작 12, 24, 36, 48개월째에 각각 12.5%, 43.8%, 63.5%, 92.7%였다. 누적 HBV DNA 음전율은 12, 24, 36, 48개월째에 각각 6.7%, 30.0%, 45.6%, 78.2%였다. 누적 HBeAg titer 2 $log_{10}$ IU/mL 감소율은 12, 24, 36, 48개월째에 각각 12.5%, 43.8%, 56.3%, 86.9%였다. 누적 HBeAg 소실률과 HBeAg 혈청 전환율은 12, 24개월째에 각각 6.7%, 22.2%였다. 연구 기간 동안 아데포비어 내성은 관찰되지 않았고 1예에서 혈뇨가 있었으나 약제 중단 후 호전되었다. 결 론: 한국의 라미부딘 내성 소아 청소년 만성 B형간염 환자에서 아데포비어의 치료는 HBeAg 혈청전환을 가속화시키며 혈청학적 간 기능을 보존하였으며 장기 사용에도 안정적이었다.

• Toxicological Research
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• 제33권4호
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• pp.343-350
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• 2017

Lamivudine belongs to the set of antiviral agents effective against hepatitis B virus infection. Given case reports on liver injuries after certain antiviral agent treatments, this study examined the effects of lamivudine on alanine aminotransferase (ALT) and total bilirubin (TB) using a medical system database. A total of 1,321 patients taking lamivudine alone or with others were evaluated using laboratory hits in an electronic medical system at Seoul National University Hospital from 2005 through 2011. The patients were grouped according to prior ALT results: G#1, ALT < 40 IU/L; G#2, 40 IU/L ${\leq}$ ALT < 120 IU/L; G#3, 120 IU/L ${\leq}$ ALT < 240 IU/L; and G#4, ALT ${\geq}$ 240 IU/L. In G#1 and G#2 patients, lamivudine or adefovir treatment decreased ALT and TB compared to prior values. In G#3 and G#4 patients with three times the upper limit of normal (ULN) ${\leq}$ ALT < 15 times the ULN, both ALT and TB were decreased after treatment with lamivudine alone, or adefovir following lamivudine therapy, indicating that lamivudine therapy ameliorated liver functions. However, in G#4 patients who experienced severely advanced hepatitis (ALT ${\geq}$ 15 times the ULN, or ${\geq}$ 600 IU/L), lamivudine augmented TBmax ($6.3{\rightarrow}13.3mg/dL$) despite a slight improvement in ALT ($839{\rightarrow}783IU/L$), indicative of exacerbation of bilirubinemia. Patients who used adefovir after lamivudine also showed a high incidence of hyperbilirubinemia when they experienced severely advanced hepatitis. Treatment with adefovir alone did not show the effect. In conclusion, lamivudine may increase the risk of hyperbilirubinemia in patients with severely advanced hepatitis, implying that caution should be exercised when using lamivudine therapy in certain patient populations.

• Clinical Pain
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• 제20권2호
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• pp.131-134
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• 2021

We report a rare case of anti-viral agent induced hypophosphatemic osteomalacia presented with localized and radicular pain. A 51-year-old man, who had been taking adefovir for chronic hepatitis, had experienced low back pain radiating to his right thigh for 2 years. With impression of lumbar disc herniation, he underwent magnetic resonance imaging and found multi-level disc herniation with facet joint synovial cysts. He received transforaminal epidural steroid injections, however, symptoms did not improve. To find other possible causes, additional tests were performed. Blood tests revealed hypophosphatemia and increased serum alkaline phosphatase, and osteoporosis was noted in dual-energy X-ray absorptiometry with multiple hot uptakes in bone scan. After replacement of adefovir to entecavir and supplement of phosphate and vitamin D, phosphate level and the clinical symptoms were improved. This is the first to report the presentation of osteomalacia due to anti-viral agent as radicular low back pain with facet synovial cysts.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제13권1호
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• pp.44-50
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• 2010

목 적: 라미부딘에 내성을 보인 소아 청소년 만성 B형 간염에서 엔테카비어 단독요법의 바이러스 억제효과를 확인하고자 하였다. 방 법: 라미부딘에 내성을 보이는 소아 청소년 만성 B형 간염 환자 23명 중 6명(남 4, 나이 15.1~24.6세, 평균 17.5세)에게 엔테카비어 1 mg으로 치료하였으며 (평균 13.4개월, 1~21.1개월) 아데포비어로 치료한 11명과 비교하였다. 치료 시작 후 HBV DNA 역가가 1 $log_{10}$ 이하, 2 $log_{10}$ 이하, 357 IU/mL 이하로 감소하는데 걸리는 기간을 각각 구하여 서로 비교하였다. 결 과: HBV DNA 역가가 2 $log_{10}$ IU/mL 이상 감소하는데 걸린 기간은 각각 2.4${\pm}$2.3개월, 9.2${\pm}$7.3개월로 (p=0.025) 두 군 간에 유의한 차이가 있었다. HBV DNA 역가가 1 $log_{10}$ IU/mL 이상 감소하는데 걸린 기간 및 357 IU/mL 이하로 감소하는데 걸린 기간은 두 군 간에 유의한 차이가 없었다. 결 론: 라미부딘 내성 소아 청소년 만성 B형 간염에서 엔테카비어 단독요법은 아데포비어 단독요법과 비교해 볼 때 HBV DNA 역가가 2 $log_{10}$ IU/mL 이상 감소하는데 걸린 기간이 유의하게 짧았다. 특별한 부작용은 관찰되지 않았다. 엔테카비어의 치료 효과를 알기 위하여 더 많은 환자를 대상으로 한 장기 치료가 필요하다.