Safety and Tolerance of Adefovir Dipivoxil in Chinese Healthy Volunteers: A PhaseⅠRandomized and Open-Label Trial

Aim To assess the safety and tolerance of adefovir dipivoxil （ADV） in Chinese healthy volunteers. Methods A total of 52 healthy volunteers, 26 males and 26 females, aged from 19 to 26 were enrolled in the study. Forty-two subjects were randomized into 5, 10, 20, 40, and 60 mg dose groups （6 - 10 subjects in each） matched by sex and weight for single-dose trial. Ten subjects were orally given 10 mg of ADV tablets once daily for 7 d for multiple-dose trial. Physical examination, vital signs examination, electrocardiography, type-B ultrasonography, chest fluoroscopy, routine blood test, routine urine test, coagulation tests, and blood biochemical test were conducted on schedule and statistically evaluated. Results Asthenia frequently occurred in multiple-dose trial, nausea, abdominal pain, and diarrhea occurred in both single- and multiple-dose trials. ALT, bilirubin, CK, and LDH were slightly elevated. All adverse reactions and laboratory abnormalities were mild, and the frequency and severity were not related to doses. Conclusion ADV is safe and well tolerated in Chinese healthy volunteers at dose of 5 - 60 mg oncedaily or 10 nag once daily for 7 d. The recommended oral dosage regimen is 10 mg once daily. Attention should be paid to renal and liver functions, CK, AMY and LDH, if we take ADV for a long period of time.

De novo combined lamivudine and adefovir dipivoxil therapy vs entecavir monotherapy for hepatitis B virus-related decompensated cirrhosis

AIM:To compare efficacy of combined lamivudine(LAM)and adefovir dipivoxil(ADV)therapy with that of entecavir(ETV)monotherapy for hepatitis B virus(HBV)-related decompensated liver cirrhosis.METHODS:A total of 120 na ve patients with HBVrelated decompensated cirrhosis participated in this study.Sixty patients were treated with combined LAM and ADV therapy(LAM+ADV group),while the other60 were treated with ETV monotherapy(ETV group)for two years.Tests for liver and kidney function,alpha-fetoprotein,HBV serum markers,HBV DNA load,prothrombin time(PT),and ultrasonography or computed tomography scan of the liver were performed every1 to 3 mo.Repeated measure ANOVA and theχ2test were performed to compare the efficacy,side effects,and the cumulative survival rates at 48 and 96 wk.RESULTS:Forty-five patients in each group were observed for 96 wk.No significant differences in HBV DNA negative rates and alanine aminotransferase(ALT)normalization rates at weeks 48(χ2=2.12 and 2.88)and96(χ2=3.21 and 3.24)between the two groups were observed.Hepatitis B e antigen seroconversion rate in the LAM+ADV group at week 96 was significantly higher in the ETV group(43.5%vs 36.4%,χ2=4.09,P<0.05).Viral breakthrough occurred in 2 cases(4.4%)by week 48 and in 3 cases(6.7%)by week 96 in the LAM+ADV group,and no viral mutation was detected.In the ETV group,viral breakthrough occurred in 1 case(2.2%)at the end of week 96.An increase in albumin(F=18.9 and 17.3),decrease in total bilirubin and in ALT(F=16.5,17.1 and 23.7,24.8),reduced PT(F=22.7 and 24.5),and improved Child-Turcotte-Pugh and the model for end-stage liver disease scores(F=18.5,17.8,and 24.2,23.8)were observed in both groups.The cumulative rates of mortality and liver transplantation were 16.7%(10/60)and 18.3%(11/60)in the LAM+ADV and ETV groups,respectively.CONCLUSION:Both LAM+ADV combination therapy and ETV monotherapy can effectively inhibit HBV replication,improve liver function,and decrease mortality.

Early kidney injury during long-term adefovir dipivoxil therapy for chronic hepatitis B

AIM: To evaluate urine β2-microglobulin(β2-M), retinol-binding protein(RBP) excretion, and renal impairment with adefovir dipivoxil(ADV) for chronic hepatitis B. METHODS: We enrolled 165 patients with chronic hepatitis B infection who were treated with ADV monotherapy(n = 90) or ADV plus lamivudine combination therapy(n = 75). An additional 165 chronic hepatitis B patients treated with entecavir were recruited as controls. We detected serum creatinine, urine β2-M, and RBP levels, and estimated the glomerular filtration rate(e GFR) at the initiation of antiviral therapy and every 6 mo for a period of five years. RESULTS: Urine β2-M abnormalities were observed in patients during the first(n = 3), second(n = 7), third(n = 11), fourth(n = 16), and fifth(n = 21) year of ADV treatment. Urinary RBP abnormalities were observed in patients during the first(n = 2), second(n = 8), third(n = 12), fourth(n = 15), and fifth(n = 22) year of ADV treatment. e GFR decreased 20%-30% from baseline in 20 patients, 30%-50% in 12 patients, and > 50% in 3 patients during the five years of treatment. Further analysis indicated that decreases in e GFR of ≥ 30% relative to the baseline level correlated significantly with urine RBP and β2-M abnormalities. In contrast, both serum creatinine and e GFR remained stable in patients treated with entecavir, and only one of these patients developed a urine β2-M abnormality, and two developed urine RBP abnormalities during the five years of treatment. CONCLUSION: Urine RBP and β2-M are biomarkers of renal injury during long-term ADV treatment for chronic hepatitis B, and indicate when treatment should be switched to entecavir.

Development of osteomalacia in a post-liver transplant patient receiving adefovir dipivoxil

We report the case of a patient treated with living donor-related liver transplantation who suffered from osteomalacia during adefovir dipivoxil (ADV)-containing antiviral therapy for lamivudine-resistant hepatitis B virus infection. The patient had generalized bone pain,with severe hypophosphatemia after 20 mo of ADV therapy. Radiographic studies demonstrated the presence of osteomalacia. The peak plasma ADV level was 38 ng/mL after administration of ADV at 10mg/day. It was also found that ADV affected the metabolism of tacrolimus,a calcineurin-inhibitor,and caused an increase in the plasma levels of tacrolimus. The disability was reversed with the withdrawal of ADV and with mineral supplementation. ADV can cause an elevation of plasma tacrolimus levels,which may be associated with renal dysfunction. High levels of ADV and tacrolimus can cause nephrotoxicity and osteomalacia. This case highlights the importance of considering a diagnosis of osteomalacia in liver transplantation recipients treated with both ADV and tacrolimus.

Surgical treatment of HCC in a patient with lamivudine-resistant hepatitis B cirrhosis with adefovir dipivoxil

We describe a 77-year-old woman with chronic hepatitis B who became resistant to lamivudine.She was started on adefovir(10 mg daily)while still continuing lamivudine therapy.Four mo later her liver function improved and serum Hepatitis B virus(HBV)-DNA level became undetectable.Three years after the start of additional adefovir treatment,hepatocellular carcinoma (HCC)was detected and the patient underwent a successful hepa-tectomy.Our findings suggest tha-t the addition of adefovir to ongoing lamivudine therapy cannot completely suppress hepatocarcinogenesis,but is useful for improving liver function in patients with lamivudine-resistant HBV-related cirrhosis,allowing HCC surgery.

Resistant mutants induced by adefovir dipivoxil in hepatitis B virus isolates

AIM: To investigate the loci of adefovir dipivoxil (ADV)-induced resistance in hepatitis B virus (HBV) isolates and optimize the management of ADV-treated patients.

Combination Therapy with Pegylated Interferon alpha-2b and Adefovir Dipivoxil in HBeAg-positive Chronic Hepatitis B versus Interferon Alone: A Prospective, Randomized Study

Currently available monotherapies of oral nucleoside/nucleotide analogs or interferon are unable to achieve a sustained and effective response in most of patients with chronic hepatitis B（CHB）. The objective of the present study was to compare the efficacy and safety of pegylated interferon（Peg-IFN） alpha-2b plus adefovir dipivoxil combination therapy versus Peg-IFN alpha-2b alone. Sixty-one HBeAg-positive chronic hepatitis B patients were randomized to receive Peg-IFN alpha-2b alone（1.5 μg/kg once weekly） or Peg-IFN alpha-2b plus adefovir（10 mg daily） for up to 52 weeks. Efficacy and safety analyses were performed on all participants who received at least one dose of study medication. The rate of HBeAg seroconversion and undetectable HBV-DNA were evaluated after 52 weeks of therapy. At the end of treatment, 11 of 30（36.7%） patients receiving combination therapy achieved HBeAg seroconversion versus 8 of 31（25.8%） in the monotherapy group（P=0.36）. In contrast, the percentage of patients with undetectable serum HBV DNA was significantly higher in the combination group than in the monotherapy group（76.7% vs. 29.0%, P〈0.001）. Thyroid dysfunction was more frequent in the combination group than in the monotherapy group（P〈0.05）. In HBeAg-positive CHB, combination of Peg-IFN alpha-2b and adefovir for 52 weeks resulted, at the end of treatment, in a higher virological response but without significant impact on the rate of HBeAg seroconversion and possibly an adverse effect on thyroid function.

Relationship Between Serum DNA Replication, Clinicopathological Characteristics and Prognosis of Hepatitis B Virus-associated Glomerulonephritis with Severe Proteinuria by Lamivudine Plus Adefovir Dipivoxil Combination Therapy

Objective To explore the relationship between HBV DNA and the clinical manifestations, pathological types, injury severity, and prognosis with HBV-GN. Methods 102 patients with HBV-GN were divided into 3 groups, according to the serum titer of the HBV DNA. 24-h urine protein excretion, and other parameters were measured. Renal biopsy were performed. The association between HBV DNA and the pathological stage of membranous nephropathy was analyzed in 78 patients with HBV-MN. 24-h urine protein excretion was used for the evaluation of the prognosis, and the relationship between HBV DNA and prognosis were analyzed. Results Several findings were demonstrated with the increase of serum HBV DNA： 24-h urine protein excretion, plasma cholesterol, and triglycerides increased significantly（P〈0.05）, while the plasma level of albumin decreased significantly（P〈0.05）; The changes of serum creatinine, C3 and C4 were found but no statistical significance. Glomerular deposition of HBVAg increased, and the pathological injury was more severe. The clinical remission rate was lower in the high replication group after treatment as compared with the low replication group（P〈0.01）. Conclusion With the increase of serum HBV DNA, the urine protein excretion and the kidney injury were more severe, and the clinical remission rate was decreased.

Short-term overlap lamivudine treatment with adefovir dipivoxil in patients with lamivudine-resistant chronic hepatitis B

AIM： To evaluate the efficacy of short-term overlap lamivudine therapy with adefovir in patients with lamivudine-resistant and naive chronic hepatitis B, we compared patients receiving overlap therapy with those receiving adefovir alone. METHODS： Eighty patients who had received lamivudine treatment for various periods and had a lamivudineo resistant liver function abnormality were enrolled. Forty of these patients received adefovir treatment combined with lamivudine treatment for ≥ 2 mo, while the other 40 received adefovir alone. We assessed the levels of hepatitis B virus （HBV） DNA at 0, 12 and 48 wk and serum alanine aminotransferase （ALT） levels after 0, 12, 24 and 48 wk of adefovir treatment in each group. RESULTS： We found serum ALT became normalized in 72 （87.5%） of the 80 patients, and HBV DNA decreased by ≥ 2 Ioglo copies/mL in 60 （75%） of the 80 patients at the end of a 48-wk treatment. HBV DNA levels were not significantly different between the groups. The improvements in serum ALT were also not significantly different between the two groups. CONCLUSION： These findings suggest short-term overlap lamivudine treatment results in no better virological and biological outcomes than non-overlap adefovir monotherapy.

De novo combination therapy with lamivudine and adefovir dipivoxil in chronic hepatitis B patients

AIM:To investigate the appropriate time for combination therapy in HBeAg positive chronic hepatitis B(CHB) patients with decompensated cirrhosis.METHODS:Thirty HBeAg positive CHB patients with decompensated cirrhosis were enrolled in the study.All of the patients were given 48 wk combination therapy with lamivudine(LAM) and adefovir dipivoxil(ADV) .Briefly,10 patients were given the de novo combination therapy with LAM and ADV,whereas the other 20 patients received ADV in addition to LAM after hepatitis B virus(HBV) genetic mutation.RESULTS:Serum alanine aminotransferase and total bilirubin were both improved in the two groups at 4,12,24 and 48 wk after treatment.Serum albumin was also improved at 24 and 48 wk after combination therapy in both groups.The serum HBV DNA level wasstill detectable in every patient in the two groups at 4 and 12 wk after combination treatment.However,in the de novo combination group,serum HBV DNA levels in 4(40%) and 9(90%) patients was decreased to below 1×10 3 copies/mL at 24 and 48 wk after the combination treatment,respectively.In parallel,serum HBV DNA levels in 2(20%) and 8(40%) patients in the add-on combination group became undetectable at 24 and 48 wk after combination treatment,respectively.Furthermore,6(60%) patients in the de novo combination group achieved HBeAg seroconversion after 48 wk treatment,whereas only 4(20%) patients in the add-on combination group achieved seroconversion.Child-Pugh score of patients in the de novo combination group was better than that of patients in the add-on combination group after 48 wk treatment.Moreover,patients in the de novo combination group had a significantly decreased serum creatinine level and elevated red blood cell counts.CONCLUSION:De novo combination therapy with LAM and ADV was better than add-on combination therapy in terms of Child-Pugh score,virus inhibition and renal function.

Adefovir dipivoxil for the treatment of lamivudine-resistant hepatitis B mutants

BACKGROUND: The recurrence of chronic hepatitis B after liver transplantation results in increased risk for graft failure and death of patients. Lamivudine has been shown to be effective in the treatment of chronic hepatitis B, but resistance to this agent is common after prolonged administration. METHODS: One patient with chronic hepatitis B virus (HBV) infection developed resistance to lamivudine after 15 months of treatment. The resistance was confirmed by mutation in the HBV DNA polymerase gene. The patient was treated subsequently with adefovir dipivoxil for 7 months. RESULT: HBV DNA and HBsAg were tested negative, but HBeAb and HBsAb were positive. CONCLUSION: This study provides an evidence that adefovir dipivoxil can be effective in the treatment of lamivudine-resistant HBV mutants.

Solid lipid nanoparticles loading adefovir dipivoxil for antiviral therapy

Herein,solid lipid nanoparticles(SLN)were proposed as a new drug delivery system for adefovir dipivoxil(ADV). The octadecylamine-fluorescein isothiocynate(ODA-FITC)was synthesized and used as a fluorescence maker to be incorporated into SLN to investigate the time-dependent cellular uptake of SLN by HepG2.2.15.The SLN of monostearin with ODA-FITC or ADV were prepared by solvent diffusion method in an aqueous system.About 15 wt%drug entrapment efficiency(EE)and 3 wt% drug loading(DL)could be reached in SLN loading ADV.Comparing with free ADV,the inhibitory effects of ADV loaded in SLN on hepatitis B surface antigen(HBsAg),hepatitis B e antigen(HBeAg)and hepatitis B virus(HBV)DNA levels in vitro were significantly enhanced.

Observation on the effect of adefovir dipivoxil in combined with lamivudine in the treatment of hepatitis B cirrhosis

Objective:To explore the effect of adefovir dipivoxil in combined with lamivudine on the liver function in patients with hepatitis B cirrhosis and the antiviral efficacy.Methods:A total of 156 patients with hepatitis B cirrhosis who were admitted in our hospital were included in the study and randomized into the treatment group and the control group with 78 cases in each group. The patients in the treatment group were given adefovir dipivoxil in combined with lamivudine, while the patients in the control group were given entecavir. After 12-month treatment, the efficacy was evaluated. The liver function, serum virology indicators, and AFP before and after treatment in the two groups were compared. The adverse reactions during the treatment process were recorded.Results: The serum GTP, ALT, AST, and TBIL levels after treatment in the two groups were significantly reduced when compared with before treatment (P<0.05);moreover, ALT and TBIL levels in the treatment group were significantly lower than those in the control group (P<0.05). HBeAg, HBV-DNA, and AFP levels after treatment in the two groups were significantly reduced when compared with before treatment (P<0.05), HBeAg and AFP levels in the treatment group were significantly lower than those in the control group (P<0.05), and the comparison of HBV-DNA between the two groups was not statistically significant (P>0.05). ALT normalization rate and HBeAg negative conversion rate after treatment in the treatment group were significantly higher than those in the control group (P<0.05). The comparison of HBV-DNA negative conversion rate and HBeAg conversion rate between the two groups was not statistically significant (P>0.05). No obvious drug adverse reactions and liver function damage occurred during the treatment process in the two groups. Conclusions:Adefovir dipivoxil in combined with lamivudine can significantly improve the liver function and serum virology indicators in patients with hepatitis B cirrhosis, with antiviral efficacy significantly superior to that by entecavir.

LAM耐药后ADV序贯治疗再耐药HBV变异株的动态变化

目的:观察阿德福韦酯(ADV)单药序贯治疗拉米夫定(LAM)耐药慢性乙型肝炎(CHB)出现再耐药患者HBV变异株的动态变化.方法:28例初始LAM治疗的CHB患者,出现LAM耐药后换用ADV单药序贯治疗再次出现不充分病毒学应答或病毒学突破.采用实时荧光定量PCR检测DNA,分析HBV DNA动态变化;采用直接PCR产物测序法检测耐药变异,分析变异模式变化.对其中2例患者系列血清进行基因克隆分析其HBV耐药株动态变化.结果:28例入选患者HBVDNA载量随耐药变异株的消长而波动:基线为(7.65±1.04)Log10 copies/mL,LAM疗程中最低值中位数为3.68Log10 copies/mL;出现病毒学突破或/和耐药变异时为(6.87±1.16)Log10 copies/mL,患者换用ADV后最低值中位数为3.78Log10 copies/mL;患者出现耐药变异模式改变或再次病毒学突破时为(6.04±0.93)Log10 copies/mL.治疗基线及两次病毒突破3个时点HBV DNA载量均数逐渐下降,且两两之间差异均有统计学意义.28例患者LAM治疗后24例发生rtM204I/V伴或不伴rtL180M等变异,4例无耐药变异;换用ADV单药序贯治疗出现病毒学突破后,进行测序检测耐药发现:LAM耐药变异13例(包括3例多重耐药),ADV耐药变异11例(包括3例多重耐药),无耐药变异7例.其中11例ADV耐药患者:rtA181V变异6例、rtA181T变异3例、rtN236T变异和rtA181V+rtN236T联合变异各1例.对2例患者血清TA克隆发现ADV耐药准种出现和LAM耐药准种消失的过程,同时发现对ADV耐药的rtI233M变异和对替诺福韦耐药的rtA194T变异.结论:ADV单药序贯治疗LAM耐药CHB出现再耐药患者HBV变异株动态变化存在5种形式,且克隆分析可观察耐药株动态变化过程和发现预存的耐药准种.

LAM和ADV长期联合后转换为替诺夫韦治疗乙型肝炎肝硬化患者疗效及其对肾功能的影响

目的探讨长期联合应用拉米夫定(LAM)和阿德福韦酯(ADV)后转换为替诺夫韦治疗乙型肝炎肝硬化患者疗效及其对肾功能的影响。方法2015年2月~2018年2月我院收治的乙型肝炎肝硬化患者130例,纳入患者均经过LAM联合ADV治疗至少5年以上(5~8年)。采用随机数字表法将患者分成观察组(n=65)和对照组(n=65)。在对照组,继续应用LAM联合ADV治疗,而在观察组,改用替诺夫韦治疗,观察12个月。采用电化学发光免疫法检测血清25-羟维生素[25-(OH)D 3]水平,使用流式细胞仪检测外周血辅助性T细胞17(Th17)和调节性T细胞(Treg)百分比,并计算Th17/Treg细胞比值。检测血清肌酐(Cr)和尿素(Urea),并计算估算的肾小球滤过率(eGFR)。结果在治疗12个月末,观察组血清HBV DNA水平为(2.3±0.7)lg IU/mL,显著低于对照组[(3.1±0.9)lg IU/mL,P<0.05],Child评分为(6.3±1.4),显著低于对照组【(8.2±1.3),P<0.05】;观察组血清25-(OH)D 3水平为(26.8±2.1)ng/ml,显著高于对照组[(22.6±1.7)ng/ml,P<0.05],外周血Treg细胞百分比为(3.4±0.6)%,显著高于对照组[(3.1±0.4)%,P<0.05],Th17细胞百分比为(2.1±0.3)%,显著高于对照组[(1.5±0.1)%,P<0.05],而Th17/Treg细胞比值为(0.3±0.1),显著低于对照组[0.4±0.1),P<0.05];观察组血清Cr水平为(0.80±0.07)mg/dl,显著低于对照组[(0.89±0.06)mg/dl,P<0.05],Urea水平为(11.27±4.36)mmol/L,显著低于对照组[(15.85±4.77)mmol/L,P<0.05],而eGFR为(103.72±11.74)m L/(mi n·1.73m^2),显著高于对照组[(90.63±13.75)mL/(min·1.73m^2),P<0.05]。结论对早期应用了LAM联合ADV治疗的乙型肝炎肝硬化患者及时转换为替诺夫韦治疗,能进一步提高血清HBV DNA转阴率,改善免疫功能,对肾功能具有保护作用,其长期疗效还需要进一步观察。

ETV或ADV初治CHB患者的2年疗效观察

目的随机、对照、开放比较恩替卡韦(ETV)或阿德福韦酯(ADV)初治慢性乙型肝炎(CHB)患者2年的疗效。方法选取2007年8月-2007年12月在沈阳市第六人民医院住院的CHB患者60例,按1∶1的比例随机分成2组,分别接受ETV 0.5 mg/d或ADV 10 mg/d口服,疗程至少104周。评价患者96周HBV DNA下降幅度、HBV DNA阴转率、ALT复常率、HBeAg血清转换率、病毒学突破率及应答不佳率。结果 96周时,ETV组HBV DNA水平较基线平均降幅为(6.05±1.99)lg拷贝/ml,高于ADV组的(4.03±3.24)lg拷贝/ml(t=2.192,P=0.005)。ETV组HBV DNA阴转率高于ADV组(80%vs 40%,χ2=10.000,P=0.002)。ALT复常率、HBeAg阳性患者HBeAg血清转换率两组比较差异无统计学意义。ETV组无病毒学突破,应答不佳率为23.3%。ADV组病毒学突破率为13.3%,应答不佳率为73.3%(χ2=-2.053、15.017,P=0.04、<0.001)。结论 ETV相对于ADV可早期快速抑制病毒。不论是ETV还是ADV,24周评估原发性无应答及48周评估部分病毒学应答是优化治疗中应关注的截点。

ADV联合多烯磷脂酰胆碱治疗CHB及对细胞因子影响

目的:研究慢性乙型肝炎(CHB)患者使用阿德福韦酯(ADV)联合多烯磷脂酰胆碱药物治疗后4种血清细胞因子白细胞介素-6(IL-6)、白细胞介素-10(IL-10)、白细胞介素-21(IL-21)和肿瘤坏死因子(TNF-α)水平的变化。方法:筛选我院就诊且符合纳入标准的CHB患者48例,其中20例单用ADV进行抗乙肝病毒治疗,28例使用ADV联合多烯磷脂酰胆碱进行治疗。分别在单用或联用药物进行抗病毒药物治疗前后检测HBV-DNA载量、HBe Ag转阴率及血清中细胞因子IL-6、IL-10、IL-21和TNF-α的含量。结果:与单用抗乙肝病毒药ADV相比,与多烯磷脂酰胆碱联合使用能更好地降低HBV-DNA载量、提高乙型肝炎E抗原(HBe Ag)转阴率,降低IL-6(P=1.08×10-3)和TNF-α(P=4.1×10-2)因子水平,同时升高IL-10(P=1.88×10-5)和IL-21(P=3.5×10-2)水平,能更好改善患者肝脏功能,差异有统计学意义。结论:将抗乙肝病毒药ADV与保肝护肝药多烯磷脂酰胆碱合用能取得更好的治疗效果,提高患者生活质量。

LAM联合ADV治疗慢性乙型肝炎的疗效及安全性分析

目的探讨拉米夫定(LAM)联合阿德福韦酯(ADV)治疗慢性乙型肝炎的疗效和安全性。方法选取慢性乙型肝炎患者76例,随机分为观察组和对照组各38例。对照组采用LAM 0.1 g/d口服治疗,观察组在对照组的基础上,加用ADV 10 mg/d口服,共治疗48周。对比两组患者治疗24周及48周时的HBV-DNA定量检测结果、HBeAg转阴率、HBeAg血清转换率、谷丙转氨酶复常率以及不良反应发生情况。结果治疗24周时,观察组的乙肝病毒载量为(5.18±1.14)log10copies/mL,对照组为(5.87±1.13)log10copies/mL,均显著低于治疗前(均P<0.05);治疗48周时,观察组的乙肝病毒载量为(3.32±0.73)log10copies/mL,对照组为(4.64±0.81)log10copies/mL,均显著低于治疗24周时(均P<0.05)。治疗48周时,观察组HBV-DNA<500copies/mL和HBV-DNA<1 000 copies/mL的转阴率均为81.58%,均显著高于对照组(47.37%和50.00%)(均P<0.05)。两组患者治疗24周时以及治疗48周时的HBeAg转阴率以及HBeAg血清学转换率对比,差异均没有显著性(均P>0.05)。治疗48周时,观察组谷丙转氨酶复常率为89.47%,显著高于对照组(P<0.05)。观察组治疗过程中有1例患者发生乙肝病毒耐药,对照组治疗过程中有4例患者发生乙肝病毒耐药。两组患者在治疗过程中均没有发生严重的不良反应。结论相对于单纯应用拉米夫定,拉米夫定联合阿德福韦酯能够更有效抑制乙肝病毒的复制,减少肝细胞损伤,稳定患者的病情,且安全性良好,值得在临床上进一步推广应用。

阿德福韦酯片的制备研究

目的:优化阿德福韦酯片的处方。方法:采用均匀设计法,以填充剂比为因素A,崩解剂为因素B,润滑剂为因素C,以溶出度相似因子作为考察指标。结果:最优化的条件为填充剂比(乳糖、预胶化淀粉比为2.6),崩解剂(5.2%交联聚维酮),润滑剂(0.5%硬脂酸钙),3批验证试验的f_(2)均大于50,与参比制剂溶出行为相似,平均累积溶出度90%以上。结论:该处方设计合理,易于操作,体外溶出度良好。