Protease inhibitors atazanavir

HIV protease inhibitors atazanavir, HepG2 Divergence in class, dislipidemia [25]... 

A microbial reduction with a Rhodococcus erythropolis strain was used by BMS scientists to prepare the chiral chlorohydrin from the chloroketone (Scheme 19.15). This intermediate is incorporated into the human immunodeficiency virus (HIV) protease inhibitor Atazanavir (26). This strain was identified through screening and provided >90% yield with a diastereomeric purity of >98% and an ee of >99%.62... 

M. Jemal, S. Rao, M. Gatz, D. Whigan, LC-AdS-AdS quantitative determination of the HIV protease inhibitor atazanavir in human PBMC practical approaches to PBMC preparation and PBMC assay design for high-throughput analysis, J. Chromatogr. B, 795 (2003) 273. 

FIGURE 16.4 (A) HIV protease inhibitor atazanavir 11. (B) Diastereoselective enzymatic... 

HlV-protease inhibitor atazanavir by liquid chromatography after solid-phase extraction. J. Chromatogr. B, 2004, 810 (1), 25-34. 

Schuster, A. Burzawa, S. Jemal, M. Loizillon, E. Couerbe, P. Whigan, D. Quantitative determination of the HIV protease inhibitor atazanavir (BMS-232632) in human plasma by liquid chromatography-tandem mass spectrometry following automated solid-phase extraction, J.Chromatogr.B, 2003, 788, 377-386. 

Hulskotte EG, Feng HP, Xuan F, van Zutven MG, Treitel MA, Hughes EA, et al. Pharmacokinetic interactions between the hepatitis C virus protease inhibitor boceprevir and ritonavir-boosted HIV-1 protease inhibitors atazanavir, darunavir, and lopinavir. Qin Infect Dis 2013 56(5) 718-26. 

TC, lamivudine ABC, abacavir APV, amprenavir AST, aspartate aminotransferase ALT, alanine aminotransferase ATV, atazanavir CBC, complete blood cell count D/C, discontinue ddl, didano-sine d4T, stavudine EFV, efavirenz FTC, emtricitabine P1BV, hepatitis B virus F1CV, hepatitis C vims HIV, human immunodeficiency virus IDV, indinavir IV, intravenous LFT, liver function tests LPV/r, lopinavir + ritonavir NNRTI, nonnucleoside reverse transcriptase inhibitor NRTI, nucleoside reverse transcriptase inhibitor NVP, nevirapine PI, protease inhibitor PT, prothrombin time T.bili, total bilirubin TDF, tenofovir disoproxiI fumarate TPV, tipranavir ULN, upper limit of normal ZDV, zidovudine. 

Protease inhibitors (amprenavir, atazanavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir) Rifampin... 

Other protease inhibitors-The coadministration of atazanavir/ritonavir and other protease inhibitors would be expected to increase exposure to the other protease inhibitor. Such coadministration is not recommended. 

Pharmacology Atazanavir is an azapeptide HIV-1 protease inhibitor. The compound selectively inhibits the virus-specific processing of viral Gag and Gag-Pol polyproteins in HIV-1-infected cells, thus preventing formation of mature virions. Pharmacokinetics ... 

Resistance/Cross-resistance Various degrees of cross-resistance among protease inhibitors have been observed. Resistance to atazanavir may not preclude the subsequent use of other protease inhibitors. 

Chemotherapy Cyclophosphamide, erlotlnlb, ifos-famide, paclitaxel, tamoxifen, vinblastine, vincristine HIV protease inhibitors Amprenavir, atazanavir, indinavir, nelfinavir, ritonavir, saquinavir HMG-CoA reductase inhibitors Atorvastatin, lovastatin, simvastatin... 

This class of antiretrovirals may be considered the most potent therapeutic agents for HIV to date. Protease inhibitors are used in combination regimens and combinations of reverse-transcriptase inhibitors and protease inhibitors have been proven most effective to decrease viral load and prolong survival. However, the protease inhibitors generally show poor penetration into the CNS and thus have no effect on aids dementia. The present Pis available for the treatment of HIV are indinavir, ritonavir, nel-finavir, saquinavir and (fos)amprenavir, atazanavir and lopinavir (in combination with ritonavir as ritonavir improves the bioavailability of lopinavir by inhibiting its metabolism in the liver by CYP3A). 

TC Lamivudine ABC Abacavir d4T Stavudine ddC Zalcitabine ddl Didanosine TDF Tenofovir ZDV Zidovudine, also abbreviated as AZT FTC Emtricitabine NVP Nevirapine DLV Delavirdine EFV Efavirenz RTV, r Ritonavir Pl/r Ritonavir boosted protease inhibitor SQV Saquinavir IDV Indinavir LPV Lopinavir NEV Nelfinavir APV Amprenavir ATV Atazanavir DRV Darunavir... 

Atazanavir is an azapeptide protease inhibitor. It is active against HIV-1. Following the binding of atazanavir to the HIV protease, the protease is no longer able to process the gag-pol polyprotein precursors. This results in the production of immature HIV particles that lack the capability to infect other cells. The resistance to the drug results from site-directed mutagenesis of viral protease. The resistance is associated with codon 50. In combination with other antiretroviral agents, atazanavir is indicated for the treatment of HIV infection. 

Barreiro P, Rendon A, Rodriguqz-Novoa S, Soriano V. 2005. Atazanavir the advent of a new generation of more convenient protease inhibitors. HIV Clin Trails. 6 51-60. 

Lipid abnormalities are a major adverse effect of HIV protease inhibitors (160). In a 48-week comparison with nelfinavir, atazanavir did not significantly increase total cholesterol, fasting LDL cholesterol or triglyceride concentrations (+6.8%, -7.1%, +1.5% respectively), while the respective concentrations rose by 28%, 31%, and 42% in those who took nelfinavir. The incidence of grade 1—4 lipodystrophy was infrequent in both groups, but this endpoint was poorly defined in this study. 

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