Tenofovir alafenamide and besifovir - kasl.org

1 alafenamide and besifovir Hyun Woong LeeDepartment of Internal Medicine, Chung-Ang University College of Medicine, Seoul, KoreaCurrent antiviral therapies have dramatically improved the long-term outcomes of patients with chronic hepatitis B virus (HBV) infection. However, persistent covalently closed circular DNA can result in a viral relapse after discontinuation of antiviral treatment. While effective therapies exist, all have specific limitations, including emergence of drug resistance and certain safety concerns associated with long-term use.

2 Furthermore, lifelong antiviral treatment is necessary for most patients, as few experience seroclearance of hepatitis B surface antigen indicative of cure. Thus, there remains a need for new antiviral therapies that are safe and effective with a high genetic barrier to (LB80380) is a novel and potent acyclic nucleotide phosphonate with a similar chemical structure to adefovir and Tenofovir (TDF). In a multicenter-randomized trial, there were no differences in the proportions of patients achieving undetectable HBV DNA, normalization of ALT or HBeAg seroconversion between besifovir and entecavir therapy.

3 Tenofovir alafenamide (TAF) is a prodrug of Tenofovir . In an in vitro study, TAF resulted in high levels of the pharmacologically active metabolite Tenofovir diphosphate than TDF. In a recent study, whatever the TAF dose, the mean change in serum HBV DNA in patients receiving TAF treatment were similar to those receiving TDF. In addition, TAF has no renal transporter-dependent cytotoxicity, which may result in an improved renal safety profile. Thus, both TAF and besifovir provide effective and safer treatment for CHB patients.

4 We hope to reach the ultimate goal of a cure to HBV in the near : besifovir ; Tenofovir alafenamide ; Chronic hepatitis B B . covalently closed circular DNA (cccDNA) . , . 2017 Single Topic Symposium46 The Korean Association for study of the LiverFigure 1. The chemical structure of LB80380 (the prodrug), LB80331 (the parent drug) and LB80317 (the active moiety).

5 20-30 . 80-90 60 . , . besifovir Tenofovir disoproxil fumarate (TDF) Tenofovir alafenamide (TAF) , . Besifovir1. besifovir (LB80380) acyclic nucleotide phosphonate ( ) , . esterase parent drug LB80331.

6 LB80331 (parent drug) LB80380 (active form) LB80317 . LB80317 oxidase (aldehyde oxidase xanthine oxidae) guanosine monophosphate . diphosphate, triphosphate DNA (Fig. 1).1,2 | Tenofovir alafenamide and , 28 HBeAg , B besifovir 240 mg/ , 4 , . HBV DNA 1 log10copies/mL besifovir 4 log10copies/mL.

7 , 30 mg (n=6) 3 log10copies/mL, 60 mg (n=6) log10copies/mL, 120 mg (n=6) log10copies/mL, 240 mg (n=6) log copies/mL . , 60 mg . , , , . , .2 , besifovir 12 , , , 2 HBV DNA besifovir (30 mg, 60 mg, 90 mg, 150 mg, 240 mg) , , , , log10copies/mL (P< ).

8 , besifovir 12 , ( ) creatinine clearance . , besifovir creatinine clearance , .3 B besifovir entecavir 48 2b , . 36 besifovir 90mg, 39 besifovir 150 mg, 39 entecavir mg . , 74% , 55% HBeAg , 80% C . HBV DNA , , log10IU/mL , ALT 128, 140, 142 U/L.

9 48 HBV DNA (<20 IU/mL) 64, 63 58%, HBV DNA , , log10IU/mL, ALT 92%, 77%, 90%, HBeAg 11%, 15%, . , , . , besifovir L-carnitine 90 mg 75%, 140 mg 97% .4 L-carnitine hypoglycemia, hypoketosis, encephalopathy 600 mg L-carnitine .4 pivalic moiety.

10 , HIV adefovir (pivalic moiety ) L-carnitine 2017 Single Topic Symposium48 The Korean Association for study of the Liver . , , 3% phosphate .5 , 2 (31 besifovir 90 mg, 28 besifo-vir 150 mg, 30 entecavir mg ) HBV DNA (<20 IU/mL) 81, 79 80%, HBV DNA , , log10IU/mL, ALT 90%, 78%, 93%, HBeAg 13%, 21%, 11%.