The cyclophilin inhibitor Debio-025 shows potent anti-hepatitis C effect in patients coinfected with hepatitis C and human immunodeficiency virus.

@article{citeulike:2801062, abstract = {Debio-025 is an oral cyclophilin (Cyp) inhibitor with potent anti-hepatitis C virus activity in vitro. Its effect on viral load as well as its influence on intracellular Cyp levels was investigated in a randomized, double-blind, placebo-controlled study. Mean hepatitis C viral load decreased significantly by 3.6 log(10) after a 14-day oral treatment with 1200 mg twice daily (P < 0.0001) with an effect against the 3 genotypes (1, 3, and 4) represented in the study. In addition, the absence of viral rebound during treatment indicates that Debio-025 has a high barrier for the selection of resistance. In Debio-025-treated patients, cyclophilin B (CypB) levels in peripheral blood mononuclear cells decreased from 67 +/- 6 (standard error) ng/mg protein (baseline) to 5 +/- 1 ng/mg protein at day 15 (P < 0.01). CONCLUSION: Debio-025 induced a strong drop in CypB levels, coinciding with the decrease in hepatitis C viral load. These are the first preliminary human data supporting the hypothesis that CypB may play an important role in hepatitis C virus replication and that Cyp inhibition is a valid target for the development of anti-hepatitis C drugs.}, address = {Department of Infectious Diseases, Medical University of Bialystok, Bialystok, Poland.}, author = {Flisiak, R. and Horban, A. and Gallay, P. and Bobardt, M. and Selvarajah, S. and Wiercinska-Drapalo, A. and Siwak, E. and Cielniak, I. and Higersberger, J. and Kierkus, J. and Aeschlimann, C. and Grosgurin, P. and Nicolas-M\'{e}tral, V. and Dumont, J. M. and Porchet, H. and Crabb\'{e}, R. and Scalfaro, P. }, citeulike-article-id = {2801062}, doi = {10.1002/hep.22131}, issn = {1527-3350}, journal = {Hepatology (Baltimore, Md.)}, month = {March}, number = {3}, pages = {817--826}, posted-at = {2008-05-15 09:56:44}, priority = {2}, title = {The cyclophilin inhibitor Debio-025 shows potent anti-hepatitis C effect in patients coinfected with hepatitis C and human immunodeficiency virus.}, url = {http://dx.doi.org/10.1002/hep.22131}, volume = {47}, year = {2008} }

TY - JOUR ID - citeulike:2801062 L3 - citeulike-article-id:2801062 TI - The cyclophilin inhibitor Debio-025 shows potent anti-hepatitis C effect in patients coinfected with hepatitis C and human immunodeficiency virus. JF - Hepatology (Baltimore, Md.) VL - 47 IS - 3 SP - 817 EP - 826 AD - Department of Infectious Diseases, Medical University of Bialystok, Bialystok, Poland. SN - 1527-3350 N2 - Debio-025 is an oral cyclophilin (Cyp) inhibitor with potent anti-hepatitis C virus activity in vitro. Its effect on viral load as well as its influence on intracellular Cyp levels was investigated in a randomized, double-blind, placebo-controlled study. Mean hepatitis C viral load decreased significantly by 3.6 log(10) after a 14-day oral treatment with 1200 mg twice daily (P < 0.0001) with an effect against the 3 genotypes (1, 3, and 4) represented in the study. In addition, the absence of viral rebound during treatment indicates that Debio-025 has a high barrier for the selection of resistance. In Debio-025-treated patients, cyclophilin B (CypB) levels in peripheral blood mononuclear cells decreased from 67 +/- 6 (standard error) ng/mg protein (baseline) to 5 +/- 1 ng/mg protein at day 15 (P < 0.01). CONCLUSION: Debio-025 induced a strong drop in CypB levels, coinciding with the decrease in hepatitis C viral load. These are the first preliminary human data supporting the hypothesis that CypB may play an important role in hepatitis C virus replication and that Cyp inhibition is a valid target for the development of anti-hepatitis C drugs. AU - Flisiak, R AU - Horban, A AU - Gallay, P AU - Bobardt, M AU - Selvarajah, S AU - Wiercinska-Drapalo, A AU - Siwak, E AU - Cielniak, I AU - Higersberger, J AU - Kierkus, J AU - Aeschlimann, C AU - Grosgurin, P AU - Nicolas-Métral, V AU - Dumont, JM AU - Porchet, H AU - Crabbé, R AU - Scalfaro, P PY - 2008/03// UR - http://dx.doi.org/10.1002/hep.22131 ER -