Pharmacokinetics of LB80331 and LB80317 following oral administration of LB80380, a new antiviral agent for chronic hepatitis B (CHB), in healthy adult subjects, CHB patients, and mice

Antimicrobial Agents and Chemotherapy

Volumn 53, Issue 5, 2009, Pages 1779-1785

  Yuen, Man Fung ^a   Lee, Sung Hack ^b   Kang, Hyang Mi ^b   Chung, Ryeol Kim ^b   Kim, John ^b,c   Ngai, Vincent ^a   Lai, Ching Lung ^a  

^a UNIVERSITY OF HONG KONG   (Hong Kong)

^b LG Chemical Ltd   (South Korea)

^c Sungkyunkwan University   (South Korea)

Author keywords

[No Author keywords available]

Indexed keywords

2 AMINO 9 (1 PHOSPHONOMETHOXYCYCLOPROPYLMETHYL)PURINE; 2 AMINO 9 (1 PHOSPHONOMETHOXYCYCLOPROPYLMETHYL)PURINE BIS(PIVALOYLOXYMETHYL) ESTER; 9 (1 PHOSPHONOMETHOXYCYCLOPROPYLMETHYL)GUANINE;

ADULT; ANIMAL EXPERIMENT; ANIMAL TISSUE; AREA UNDER THE CURVE; ARTICLE; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DIET RESTRICTION; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG DOSE ESCALATION; DRUG DOSE REGIMEN; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG LIVER LEVEL; DRUG METABOLISM; DRUG SAFETY; DRUG TOLERABILITY; FEMALE; FOOD DRUG INTERACTION; HEPATITIS B; HUMAN; HUMAN EXPERIMENT; LIPID DIET; MALE; MAXIMUM PLASMA CONCENTRATION; MOUSE; MULTIPLE DRUG DOSE; NONHUMAN; NORMAL HUMAN; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PHOSPHORYLATION; PLASMA CONCENTRATION-TIME CURVE; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SINGLE DRUG DOSE; STEADY STATE; TIME TO MAXIMUM PLASMA CONCENTRATION; TISSUE DISTRIBUTION; UNSPECIFIED SIDE EFFECT;

ADMINISTRATION, ORAL; ADOLESCENT; ADULT; ANIMALS; CLINICAL TRIALS, PHASE I AS TOPIC; CLINICAL TRIALS, PHASE II AS TOPIC; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; FEMALE; HEPACIVIRUS; HEPATITIS B, CHRONIC; HUMANS; LIVER; MALE; MICE; MIDDLE AGED; NUCLEOTIDES; PRODRUGS; RANDOMIZED CONTROLLED TRIALS AS TOPIC; TREATMENT OUTCOME; YOUNG ADULT;

EID: 66149096185     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.01290-08     Document Type: Article

References (13)

1. Chang, T. T., R. G. Gish, R. de Man, A. Gadano, J. Sollano, Y. C. Chao, A. S. Lok, K. H. Han, Z. Goodman, J. Zhu, A. Cross, D. DeHertogh, R. Wilber, R. Colonno, D. Apelian, and the BEHoLD AI463022 Study Group. 2006. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. N. Engl. J. Med. 354:1001-1010.
2. Gough, K., M. Hutchison, O. Keene, B. Byrom, S. Ellis, L. Lacey, and J. Mckellar. 1995. Assessment of dose proportionality: report from the statisticians in the pharmaceutical industry/pharmacokinetics UK joint working party. Drug Information J. 29:1039-1048.
3. Hadziyannis, S. J., N. C. Tassopoulos, E. J. Heathcote, T. T. Chang, G. Kitis, M. Rizzetto, P. Marcellin, S. G. Lim, Z. Goodman, J. Ma, C. L. Brosgart, K. Borroto-Esoda, S. Arterburn, S. L. Chuck, and the Adefovir Dipivoxil 438 Study Group. 2006. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years. Gastroenterology 131:1743-1751.
4. Jakobsen, M. R., H. Arildsen, H. B. Krarup, M. Tolstrup, L. Østergaard, and A. L. Laursen. 2008. Entecavir therapy induces de novo HIV reverse-transcriptase M184V mutation in an antiretroviral therapy-naive patient. Clin. Infect. Dis. 46:e88-e91.
5. Lai, C. L., E. Gane, C. W. Hsu, S. Thongsawat, Y. Wang, Y. Chen, E. J. Heathcote, J. Rasenack, N. Bzowej, N. Naoumov, S. Zeuzem, A. Di Biscegli, G. C. Chao, A. F. Constance, and N. Brown. 2006. Two-year results from the GLOBE trial in patients with hepatitis B: greater clinical and antiviral efficacy for telbivudine (Ldt) vs. lamivudine. Hepatology 44(4 Suppl. 1):222A.
6. Lai, C. L., E. Gane, Y. F. Liaw, C. W. Hsu, S. Thongsawat, Y. Wang, Y. Chen, E. J. Heathcote, J. Rasenack, N. Bzowej, N. V. Naoumov, A. M. Di Bisceglie, S. Zeuzem, Y. M. Moon, Z. Goodman, G. Chao, B. F. Constance, N. A. Brown, and the Globe Study Group. 2007. Telbivudine versus lamivudine in patients with chronic hepatitis B. N. Engl. J. Med. 357:2576-2588.
7. Lai, C. L., K. H. Han, S. K. Yoon, S. H. Um, M. F. Yuen, H. S. Kim, H. R. Kim, H. C. Chung, C. R. Kim, P. Hsyu, D. Averett, and J. Kim. 2005. Interim report for a phase II, multi-centre, dose-escalating study of LB80380/ANA380 in hepatitis B patients with lamivudine-resistant YMDD mutant HBV. J. Hepatol 42(Suppl. 2):72A.
8. Lai, C. L., V. Ratziu, M. F. Yuen, and T. Poynard. 2003. Viral hepatitis B. Lancet 362:2089-2094. (Pubitemid 38032767)
9. Lai, C. L., D. Shouval, A. S. Lok, T. T. Chang, H. Cheinquer, Z. Goodman, D. DeHertogh, R. Wilber, R. C. Zink, A. Cross, R. Colonno, L. Fernandes, and the BEHoLD AI463027 Study Group. 2006. Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B. N. Engl. J. Med. 354:1011-1020.
10. Min, C. H., C. R. Kim, K. Steffy, D. Averett, S. Locarnini, and T. Shaw. 2007. The active metabolite of LB80380/ANA380, a novel nucleotide analog, exhibits activity in vitro against multiple clinically relevant hepatitis B virus mutants. J. Hepatol. 46(Suppl. 1):S159.
11. Tenney, D. J., K. A. Pokornowski, R. E. Rose, C. J. Baldick, B. J. Eggers, J. Fang, J. Y. Yang, D. Xu, H. Brett-Smith, and R. J. Colonno. 2008. Entecavir at five years shows long-term maintenance of high genetic barrier to hepatitis B virus resistance. Hepatol. Int. 2:A88-A89.
12. Yuen, M. F., J. Kim, C. R. Kim, V. Ngai, J. C. H. Yuen, C. Min, H. M. Kang, B. S. Shin, S. D. Yoo, and C. L. Lai. 2006. Dose-finding study of oral LB80380 in HBeAg-positive patients with chronic hepatitis B. Antivir. Ther. 11:977-983.
13. Yuen, M. F., W. K. Seto, D. H. Chow, K. Tsui, D. K. Wong, V. W. Ngai, B. C. Wong, J. Fung, J. C. Yuen, and C. L. Lai. 2007. Long-term lamivudine therapy reduces the risk of long-term complications of chronic hepatitis B infection even in patients without advanced disease. Antivir. Ther. 12:1295-1303.