scholarly journals Ex Vivo and In Vitro Effect of Human Immunodeficiency Virus Protease Inhibitors on Neutrophil Apoptosis

2000 ◽  
Vol 182 (5) ◽  
pp. 1536-1539 ◽  
Author(s):  
Claudio M. Mastroianni ◽  
Fabio Mengoni ◽  
Miriam Lichtner ◽  
Claudia D'Agostino ◽  
Gabriella d'Ettorre ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Protease Inhibitors ◽  
Ex Vivo ◽  
Neutrophil Apoptosis ◽  
Human Immunodeficiency Virus Protease ◽  
Immunodeficiency Virus ◽  
Vitro Effect

scholarly journals Effects of Human Immunodeficiency Virus Protease Inhibitors on the Intestinal Absorption of Tenofovir Disoproxil Fumarate In Vitro

2007 ◽  
Vol 51 (10) ◽  
pp. 3498-3504 ◽  
Author(s):  
Leah Tong ◽  
Truc K. Phan ◽  
Kelly L. Robinson ◽  
Darius Babusis ◽  
Robert Strab ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Interactions ◽  
Intestinal Absorption ◽  
Protease Inhibitors ◽  
Plasma Levels ◽  
Human Immunodeficiency Virus Protease ◽  
Mdckii Cells ◽  
Immunodeficiency Virus ◽  
Secretory Transport

ABSTRACT Human immunodeficiency virus protease inhibitors (PIs) modestly affect the plasma pharmacokinetics of tenofovir (TFV; −15% to +37% change in exposure) following coadministration with the oral prodrug TFV disoproxil fumarate (TDF) by a previously undefined mechanism. TDF permeation was found to be reduced by the combined action of ester cleavage and efflux transport in vitro. Saturable TDF efflux observed in Caco-2 cells suggests that at pharmacologically relevant intestinal concentrations, transport has only a limited effect on TDF absorption, thus minimizing the magnitude of potential intestinal drug interactions. Most tested PIs increased apical-to-basolateral TDF permeation and decreased secretory transport in MDCKII cells overexpressing P-glycoprotein (Pgp; MDCKII-MDR1 cells) and Caco-2 cells. PIs were found to cause a multifactorial effect on the barriers to TDF absorption. All PIs showed similar levels of inhibition of esterase-dependent degradation of TDF in an intestinal subcellular fraction, except for amprenavir, which was found to be a weaker inhibitor. All PIs caused a dose-dependent increase in the accumulation of a model Pgp substrate in MDCKII-MDR1 cells. Pgp inhibition constants ranged from 10.3 μM (lopinavir) to >100 μM (amprenavir, indinavir, and darunavir). Analogous to hepatic cytochrome P450-mediated drug interactions, we propose that the relative differences in perturbations in TFV plasma levels when TDF is coadministered with PIs are based in part on the net effect of inhibition and induction of intestinal Pgp by PIs. Combined with prior studies, these findings indicate that intestinal absorption is the mechanism for changes in TFV plasma levels when TDF is coadministered with PIs.

scholarly journals In Vitro Activity of Human Immunodeficiency Virus Protease Inhibitors againstPneumocystis carinii

2000 ◽  
Vol 181 (5) ◽  
pp. 1629-1634 ◽  
Author(s):  
Chiara Atzori ◽  
Elena Angeli ◽  
Annalisa Mainini ◽  
Fiorenza Agostoni ◽  
Valeria Micheli ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Protease Inhibitors ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Human Immunodeficiency Virus Protease ◽  
Immunodeficiency Virus

scholarly journals Synergy of Human Immunodeficiency Virus Protease Inhibitors with Chloroquine against Plasmodium falciparum In Vitro and Plasmodium chabaudi In Vivo

2008 ◽  
Vol 52 (7) ◽  
pp. 2653-2656 ◽  
Author(s):  
Zhengxiang He ◽  
Li Qin ◽  
Lili Chen ◽  
Nanzheng Peng ◽  
Jianlan You ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Plasmodium Falciparum ◽  
Protease Inhibitors ◽  
Plasmodium Chabaudi ◽  
Malaria Parasites ◽  
Human Immunodeficiency Virus Protease ◽  
Immunodeficiency Virus ◽  
Antimalarial Action

ABSTRACT The synergy of the activities between chloroquine and various human immunodeficiency virus protease inhibitors was investigated in chloroquine-resistant and -sensitive malaria parasites. In both in vitro and in vivo assay systems, ritonavir was found to be the most potent in potentiating the antimalarial action of chloroquine.

scholarly journals Synergistic Interactions of the Antiretroviral Protease Inhibitors Saquinavir and Ritonavir with Chloroquine and Mefloquine against Plasmodium falciparum In Vitro

2006 ◽  
Vol 51 (2) ◽  
pp. 759-762 ◽  
Author(s):  
T. S. Skinner-Adams ◽  
K. T. Andrews ◽  
L. Melville ◽  
J. McCarthy ◽  
D. L. Gardiner
Keyword(s):  
Human Immunodeficiency Virus ◽  
Plasmodium Falciparum ◽  
Protease Inhibitors ◽  
Antimalarial Activity ◽  
Digestive Vacuole ◽  
Synergistic Interactions ◽  
Human Immunodeficiency Virus Protease ◽  
Immunodeficiency Virus ◽  
Pepstatin A

ABSTRACT The antimalarial activity of several antiretroviral protease inhibitor combinations was investigated. Data demonstrate that ritonavir and saquinavir behave synergistically with chloroquine and mefloquine. These data, and interactions with pepstatin-A, E-64, and bestatin, suggest that human immunodeficiency virus protease inhibitors do not target digestive-vacuole plasmepsins.

In Vitro and In Vivo Anticandidal Activity of Human Immunodeficiency Virus Protease Inhibitors

1999 ◽  
Vol 180 (2) ◽  
pp. 448-453 ◽  
Author(s):  
Antonio Cassone ◽  
Flavia De Bernardis ◽  
Antonella Torosantucci ◽  
Evelina Tacconelli ◽  
Mario Tumbarello ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Protease Inhibitors ◽  
Human Immunodeficiency Virus Protease ◽  
Immunodeficiency Virus ◽  
Anticandidal Activity

scholarly journals Multiple Mutations in the Human Immunodeficiency Virus Protease Gene Are Responsible for Decreased Susceptibility to Protease Inhibitors

1995 ◽  
Vol 6 (2) ◽  
pp. 80-88 ◽  
Author(s):  
R. W. King ◽  
S. Garber ◽  
D. L. Winslow ◽  
C. Reid ◽  
L. T. Bacheler ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Protease Inhibitors ◽  
Clinical Isolate ◽  
Protease Gene ◽  
Human Immunodeficiency Virus Protease ◽  
Fold Reduction ◽  
Antiretroviral Drug ◽  
Immunodeficiency Virus ◽  
Hiv 1

The protease (PR) of the human immunodeficiency virus (HIV) is essential for replication of the virus, and accordingly has become an attractive target for the development of an antiretroviral drug. We have previously reported that passage of HIV-1 in the presence of increasing concentrations of the C-2 symmetrical, linear diol P9941 resulted in the isolation of virus with a valine-to-alanine change at position 82 (V82A) of the PR, and reduced sensitivity to certain PR inhibitors. In this study, we passaged four different variants of HIV-1 in increasing concentrations of XM323, and isolated variants with reduced sensitivity to inhibitors of PR. Twenty-three passages of HIV-1 (RF) in the presence of XM323 resulted in a variant that exhibited an approximately 100-fold reduction in susceptibility to XM323 and that contained V82F and I84V changes. When two other viruses, HIV-1 (RF41D2) and HIV-1(RF41E4), previously derived from HIV-1 (RF) by passage in the presence of P9941, were passaged in the presence of XM323, variants with V82A/L97V and M46L/V82A/L97V changes, respectively, were obtained. The M46L/V82A/L97V variant showed a 6-fold reduction in sensitivity to XM323, whereas the susceptibility of the V82A/L97V mutant remained unchanged. Seventeen passages of a clinical isolate of HIV-1, HIV-1 (Pat.E), in the presence of XM323 produced a V82F/L97V mutant with an approximately 9-fold reduction in sensitivity to XM323.

Sign in / Sign up

Export Citation Format

Share Document