BACKGROUND: Currently, more and more nucleos(t)ide analogs are appearing as therapeutic options in the treatment of chronic hepatitis B (CHB). Their efficacy and safety profile in hepatitis B virus (HBV) infection hav...BACKGROUND: Currently, more and more nucleos(t)ide analogs are appearing as therapeutic options in the treatment of chronic hepatitis B (CHB). Their efficacy and safety profile in hepatitis B virus (HBV) infection have already been studied in detail worldwide. This review summarizes the efficacy of lamivudine, adefovir, entecavir and newer antiviral agents such as emtricitabine, telbivudine and clevudine in the treatment of hepatitis B in different clinical situations. DATA SOURCES: An English-language literature search using OVID and MEDLINE was performed and a total of 40 articles on the treatment of chronic hepatitis with nucleos(t)ide analogues were selected. RESULTS: Nucleos(t)ide analogs such as lamivudine, adefovir and entecavir are well tolerated and induce a decrease in serum HBV-DNA levels associated with normalization of serum alanine aminotransferase (ALT) levels. But their sustained response with HBeAg to anti-HBe seroconversion is rarely obtained and HBsAg loss is exceptional. The response is maintained during therapy which needs to be continued indefinitely in the majority of patients since withdrawal of treatment is generally followed by a rapid reactivation of hepatitis B. However, drug resistant mutations can be induced in long-term treatment. Other newer antiviral agents such as emtricitabine, telbivudine and clevudine in the treatment of hepatitis B are still under phaseⅡorⅢclinical trials. CONCLUSIONS: Nucleos(t)ide analogs play an important role in the therapy of hepatitis B now and in the future. Lamivudine is limited by the frequent emergence of drugresistant (HBV) mutants (YMDD). Adefovir and entecavir appear to be effective against both YMDD mutation and wild type. Therapeutic options against hepatitis B virus remain a major clinical challenge.展开更多
A simple, sensitive and rapid stability indicating reverse phase ultra performance liquid chromatography (RP-UPLC) method was developed and validated for the determination of Emtricitabine (EMT) and Tenofovir disoprox...A simple, sensitive and rapid stability indicating reverse phase ultra performance liquid chromatography (RP-UPLC) method was developed and validated for the determination of Emtricitabine (EMT) and Tenofovir disoproxil fumarate (TDF) in pure and tablet dosage forms. The chromatographic separation was achieved by using Waters (Alliance) UPLC system equipped with auto-sampler and photo diode array detector. A volume of 5 μL of standard or test was injected into the column and the components were separated by using the mixture of 0.68% potassium dihydrogen orthophosphate buffer of pH = 6 and methanol in the ratio 45:55 v/v as mobile phase at a flow rate of 1.2 mL/min through BEH C18 (100 mm × 2.1, 1.8 μm) at ambient temperature and were detected at a wavelength of 261 nm. System suitable parameters such as plate count and tailing factor for EMT and TDF were found to be 2427 & 3685, 1.16 & 1.23 respectively, and resolution between EMT and TDF peaks was found to be 3.12. The chromatographic parameters like retention time, peak area and peak height of EMT and TDF were found to be 0.684 & 0.930, 694,200 & 8,778,000 and 272,881 & 3685 respectively. Percent of assay of EMT and TDF in bulk and dosage forms was determined and found to be 101.48 and 103.22 respectively. Study of degradation was examined and found that the drugs were stable under degradation conditions. The present method was developed keeping the principles of green chemistry by using eco-friendly solvent methanol in mobile phase. The developed method was found to be simple, rapid and applied for the analysis of Truvada;therefore the proposed method is recommended for the analysis of EMT and TDF in pure and tablet dosage forms in any quality control laboratories.展开更多
Purpose: Tenofovir disoproxil fumarate (TEN) and emtricitabine (EMT) are both second generation ant-retroviral drugs used in the “treatment” of HIV/AIDS. The aim of this study is to establish the physic-chemical pro...Purpose: Tenofovir disoproxil fumarate (TEN) and emtricitabine (EMT) are both second generation ant-retroviral drugs used in the “treatment” of HIV/AIDS. The aim of this study is to establish the physic-chemical properties of their reaction with chloranilic acid in different solvent systems and to justify the chemical basis for simultaneous quantitative determination of these drugs in their combined formulation. Method: TEN and EMT were individually isolated from their single formulations and purified by chromatography to obtain secondary standard. Purity of the isolates were tested for by comparison with literature values. Stock solution of chloranilic acid (CA) [3.0 × 10﹣3 M] was prepared in the following solvents of different polarities: ethanol, acetonitrile, ethylacetate, chloroform and hexane. Equal volumes of CA and TEN [3.0 × 10﹣2 M] and EMT [3.0 × 10﹣2 M] dissolved in different solvents were mixed whereby colored products were observed. Absorption maxima were determined. Calibration curves were generated and validated. Quantitative simultaneous determination of TEN and EMT was determined by standard protocol. Stoichiometric relationships between the drugs and CA were established. Equilibrium constants were determined at different temperatures from which the Gibb’s free energies were calculated. Arrhenius equation was used to calculate the enthalpy, entropy was similarly calculated. Results: Absorption maxima of CA in different solvents are as follows: Ethanol 310 nm;Acetonitrile 330 nm;Ethyl acetate 340 nm;Chloroform 350 nm and hexane 310 nm. The complex of CA and TEN in the different solvents are: Alcohol 525 nm, Acetonitrile 500 nm;Ethyl acetate 505 nm;Chloroform 510 nm and hexane 515 nm. For EMT complex absorption maxima are: Alcohol 510 nm;Acetonitrile 515 nm’ Ethyl acetate 520 nm’ Chloroform 505 nm and hexane 530 nm. Simultaneous quantitative recovery values for TEN are: Ethanol;97.89% ± 1.21;Acetonitrile 101.17 V 1.51%;Ethyl acetate 96.55% ± 0.71%;Chloroform 99.11% ± 0.34% and展开更多
文摘BACKGROUND: Currently, more and more nucleos(t)ide analogs are appearing as therapeutic options in the treatment of chronic hepatitis B (CHB). Their efficacy and safety profile in hepatitis B virus (HBV) infection have already been studied in detail worldwide. This review summarizes the efficacy of lamivudine, adefovir, entecavir and newer antiviral agents such as emtricitabine, telbivudine and clevudine in the treatment of hepatitis B in different clinical situations. DATA SOURCES: An English-language literature search using OVID and MEDLINE was performed and a total of 40 articles on the treatment of chronic hepatitis with nucleos(t)ide analogues were selected. RESULTS: Nucleos(t)ide analogs such as lamivudine, adefovir and entecavir are well tolerated and induce a decrease in serum HBV-DNA levels associated with normalization of serum alanine aminotransferase (ALT) levels. But their sustained response with HBeAg to anti-HBe seroconversion is rarely obtained and HBsAg loss is exceptional. The response is maintained during therapy which needs to be continued indefinitely in the majority of patients since withdrawal of treatment is generally followed by a rapid reactivation of hepatitis B. However, drug resistant mutations can be induced in long-term treatment. Other newer antiviral agents such as emtricitabine, telbivudine and clevudine in the treatment of hepatitis B are still under phaseⅡorⅢclinical trials. CONCLUSIONS: Nucleos(t)ide analogs play an important role in the therapy of hepatitis B now and in the future. Lamivudine is limited by the frequent emergence of drugresistant (HBV) mutants (YMDD). Adefovir and entecavir appear to be effective against both YMDD mutation and wild type. Therapeutic options against hepatitis B virus remain a major clinical challenge.
文摘A simple, sensitive and rapid stability indicating reverse phase ultra performance liquid chromatography (RP-UPLC) method was developed and validated for the determination of Emtricitabine (EMT) and Tenofovir disoproxil fumarate (TDF) in pure and tablet dosage forms. The chromatographic separation was achieved by using Waters (Alliance) UPLC system equipped with auto-sampler and photo diode array detector. A volume of 5 μL of standard or test was injected into the column and the components were separated by using the mixture of 0.68% potassium dihydrogen orthophosphate buffer of pH = 6 and methanol in the ratio 45:55 v/v as mobile phase at a flow rate of 1.2 mL/min through BEH C18 (100 mm × 2.1, 1.8 μm) at ambient temperature and were detected at a wavelength of 261 nm. System suitable parameters such as plate count and tailing factor for EMT and TDF were found to be 2427 & 3685, 1.16 & 1.23 respectively, and resolution between EMT and TDF peaks was found to be 3.12. The chromatographic parameters like retention time, peak area and peak height of EMT and TDF were found to be 0.684 & 0.930, 694,200 & 8,778,000 and 272,881 & 3685 respectively. Percent of assay of EMT and TDF in bulk and dosage forms was determined and found to be 101.48 and 103.22 respectively. Study of degradation was examined and found that the drugs were stable under degradation conditions. The present method was developed keeping the principles of green chemistry by using eco-friendly solvent methanol in mobile phase. The developed method was found to be simple, rapid and applied for the analysis of Truvada;therefore the proposed method is recommended for the analysis of EMT and TDF in pure and tablet dosage forms in any quality control laboratories.
文摘Purpose: Tenofovir disoproxil fumarate (TEN) and emtricitabine (EMT) are both second generation ant-retroviral drugs used in the “treatment” of HIV/AIDS. The aim of this study is to establish the physic-chemical properties of their reaction with chloranilic acid in different solvent systems and to justify the chemical basis for simultaneous quantitative determination of these drugs in their combined formulation. Method: TEN and EMT were individually isolated from their single formulations and purified by chromatography to obtain secondary standard. Purity of the isolates were tested for by comparison with literature values. Stock solution of chloranilic acid (CA) [3.0 × 10﹣3 M] was prepared in the following solvents of different polarities: ethanol, acetonitrile, ethylacetate, chloroform and hexane. Equal volumes of CA and TEN [3.0 × 10﹣2 M] and EMT [3.0 × 10﹣2 M] dissolved in different solvents were mixed whereby colored products were observed. Absorption maxima were determined. Calibration curves were generated and validated. Quantitative simultaneous determination of TEN and EMT was determined by standard protocol. Stoichiometric relationships between the drugs and CA were established. Equilibrium constants were determined at different temperatures from which the Gibb’s free energies were calculated. Arrhenius equation was used to calculate the enthalpy, entropy was similarly calculated. Results: Absorption maxima of CA in different solvents are as follows: Ethanol 310 nm;Acetonitrile 330 nm;Ethyl acetate 340 nm;Chloroform 350 nm and hexane 310 nm. The complex of CA and TEN in the different solvents are: Alcohol 525 nm, Acetonitrile 500 nm;Ethyl acetate 505 nm;Chloroform 510 nm and hexane 515 nm. For EMT complex absorption maxima are: Alcohol 510 nm;Acetonitrile 515 nm’ Ethyl acetate 520 nm’ Chloroform 505 nm and hexane 530 nm. Simultaneous quantitative recovery values for TEN are: Ethanol;97.89% ± 1.21;Acetonitrile 101.17 V 1.51%;Ethyl acetate 96.55% ± 0.71%;Chloroform 99.11% ± 0.34% and
