The Experts below are selected from a list of 33 Experts worldwide ranked by ideXlab platform
Sharon Walmsley - One of the best experts on this subject based on the ideXlab platform.
-
Lopinavir Plus Ritonavir a novel protease inhibitor combination for hiv infections
Expert Review of Anti-infective Therapy, 2007Co-Authors: Sharon WalmsleyAbstract:Lopinavir is a protease inhibitor (PI) for the treatment of HIV infection that was specifically designed to overcome the shortcomings of earlier agents in this class. It is the only PI coformulated with Ritonavir, whose pharmacological boosting effect results in a highly potent, well-tolerated, clinically effective antiretroviral agent with a high genetic barrier to resistance. Lopinavir/Ritonavir is a recommended first-line option for antiretroviral-naive patients initiating PI-based therapy, and has an equally important role in the management of treatment-experienced individuals. Its favorable pharmacological and clinical characteristics have recently prompted investigators to explore its potential novel applications in HIV monotherapy and double-boosted regimens.
Mairin Ryan - One of the best experts on this subject based on the ideXlab platform.
-
steady state pharmacokinetics of Lopinavir Plus Ritonavir when administered under different meal conditions in hiv infected ugandan adults
Journal of Acquired Immune Deficiency Syndromes, 2012Co-Authors: Mohammed Lamorde, Pauline Byakikakibwika, Marta Boffito, Lillian Nabukeera, Jonathan Mayito, Jasper Ogwalokeng, J Tjia, D J Back, Saye Khoo, Mairin RyanAbstract:: We investigated the effect of food on the steady-state pharmacokinetics of Lopinavir and Ritonavir in 12 Ugandan patients receiving Lopinavir coformulated with Ritonavir (LPV/r) tablets using a crossover design. Intensive pharmacokinetic sampling was performed 7 days apart after LPV/r dosing under moderate fat, high fat, and fasted meal conditions. Lopinavir and Ritonavir concentrations were determined by liquid chromatography and tandem mass spectrometry. Compared with the fasted state, a high fat meal reduced Lopinavir and Ritonavir area under the curve by 14% and 29%, respectively. With a moderate fat meal, area under the curve for both drugs was similar to the fasted state.
Joseph A Kovacs - One of the best experts on this subject based on the ideXlab platform.
-
echinacea purpurea significantly induces cytochrome p450 3a activity but does not alter Lopinavir Ritonavir exposure in healthy subjects
Pharmacotherapy, 2010Co-Authors: Scott R Penzak, Sarah M Robertson, Jennifer D Hunt, Cheryl Chairez, Christine Y Malati, Raul M Alfaro, James M Stevenson, Joseph A KovacsAbstract:Despite the success of potent combination antiretroviral (ARV) therapy, complementary and alternative medications (CAM) remain widely used by patients with HIV infection. Indeed, more than half of HIV infected patients report using CAM at some point in time.1–4 Patients with HIV infection typically use CAM for symptomatic relief of side effects secondary to ARV therapy and/or general health benefits. Unfortunately, the co-administration of CAM and ARV medications can place patients at risk for clinically significant drug drug interactions. Because HIV protease inhibitors are primarily metabolized by cytochrome P450 (CYP) 3A4, herbal preparations that modulate this metabolic pathway have the potential to alter protease inhibitor pharmacokinetics potentially resulting in reduced ARV efficacy or increased toxicity.1 Piscitelli et al. found that St. John’s wort decreased the systemic exposure of the HIV protease inhibitor indinavir by 57% during coadministration.5 In a separate study by the same investigators, three weeks of garlic caplet supplementation decreased the area under the concentration versus time curve (AUC) of saquinavir, another HIV protease inhibitor, by 51%.6 In spite of the potential for clinically relevant interactions between CAM and ARVs, relatively few herbal products have been tested for their effects on ARV drug disposition in vivo; one such herbal supplement that has not been assessed for its influence on ARV pharmacokinetics is Echinacea purpurea. E purpurea is predominantly used to prevent and treat the common cold, influenza, and upper respiratory tract infections.7–9 In the setting of HIV infection, E. purpurea may be taken for its immunomodulatory and antiviral effects.1 Of note, Echinacea products ranked behind garlic as the second top-selling herbal dietary supplement in the food, drug, and mass market channel in the United States in 2005 with over 21 million U.S. dollars in sales.10 At least two studies have assessed the influence of E purpurea root on CYP3A activity in humans.11,12 Using single doses of both oral and iv midazolam as a probe for intestinal and hepatic CYP3A activity, respectively, Gorski et al. observed an 85% increase in the intestinal availability of midazolam (P=0.015) and a 15% reduction in the hepatic availability of the drug (P= 0.006) after 1600 mg (total daily dose) of E purpurea administration for 8 days.11 These data suggest that E purpurea selectively alters the catalytic activity of CYP3A in the liver vs. intestine. Conversely, Gurley et al. found that 28 days of E purpurea whole plant extract administration did not significantly alter CYP3A metabolic serum ratios of 1-hydroxymidazolam:midazolam collected one hr post-dose in 12 healthy volunteers.12 To this end, it is difficult to predict the influence of E purpurea on the pharmacokinetics of CYP3A substrates such as the HIV protease inhibitors. The presence or absence of such interactions may depend on the relative extraction of the coadministered drug by hepatic and intestinal CYP3A. Due to the potentially serious consequences of a drug-drug interaction between E purpurea and HIV protease inhibitors (i.e virologic and/or immunologic failure or drug toxicity) the current study was designed to assess the influence of E purpurea on the steady state pharmacokinetics of Lopinavir Plus Ritonavir in healthy human volunteers.
Mohammed Lamorde - One of the best experts on this subject based on the ideXlab platform.
-
steady state pharmacokinetics of Lopinavir Plus Ritonavir when administered under different meal conditions in hiv infected ugandan adults
Journal of Acquired Immune Deficiency Syndromes, 2012Co-Authors: Mohammed Lamorde, Pauline Byakikakibwika, Marta Boffito, Lillian Nabukeera, Jonathan Mayito, Jasper Ogwalokeng, J Tjia, D J Back, Saye Khoo, Mairin RyanAbstract:: We investigated the effect of food on the steady-state pharmacokinetics of Lopinavir and Ritonavir in 12 Ugandan patients receiving Lopinavir coformulated with Ritonavir (LPV/r) tablets using a crossover design. Intensive pharmacokinetic sampling was performed 7 days apart after LPV/r dosing under moderate fat, high fat, and fasted meal conditions. Lopinavir and Ritonavir concentrations were determined by liquid chromatography and tandem mass spectrometry. Compared with the fasted state, a high fat meal reduced Lopinavir and Ritonavir area under the curve by 14% and 29%, respectively. With a moderate fat meal, area under the curve for both drugs was similar to the fasted state.
Scott R Penzak - One of the best experts on this subject based on the ideXlab platform.
-
echinacea purpurea significantly induces cytochrome p450 3a activity but does not alter Lopinavir Ritonavir exposure in healthy subjects
Pharmacotherapy, 2010Co-Authors: Scott R Penzak, Sarah M Robertson, Jennifer D Hunt, Cheryl Chairez, Christine Y Malati, Raul M Alfaro, James M Stevenson, Joseph A KovacsAbstract:Despite the success of potent combination antiretroviral (ARV) therapy, complementary and alternative medications (CAM) remain widely used by patients with HIV infection. Indeed, more than half of HIV infected patients report using CAM at some point in time.1–4 Patients with HIV infection typically use CAM for symptomatic relief of side effects secondary to ARV therapy and/or general health benefits. Unfortunately, the co-administration of CAM and ARV medications can place patients at risk for clinically significant drug drug interactions. Because HIV protease inhibitors are primarily metabolized by cytochrome P450 (CYP) 3A4, herbal preparations that modulate this metabolic pathway have the potential to alter protease inhibitor pharmacokinetics potentially resulting in reduced ARV efficacy or increased toxicity.1 Piscitelli et al. found that St. John’s wort decreased the systemic exposure of the HIV protease inhibitor indinavir by 57% during coadministration.5 In a separate study by the same investigators, three weeks of garlic caplet supplementation decreased the area under the concentration versus time curve (AUC) of saquinavir, another HIV protease inhibitor, by 51%.6 In spite of the potential for clinically relevant interactions between CAM and ARVs, relatively few herbal products have been tested for their effects on ARV drug disposition in vivo; one such herbal supplement that has not been assessed for its influence on ARV pharmacokinetics is Echinacea purpurea. E purpurea is predominantly used to prevent and treat the common cold, influenza, and upper respiratory tract infections.7–9 In the setting of HIV infection, E. purpurea may be taken for its immunomodulatory and antiviral effects.1 Of note, Echinacea products ranked behind garlic as the second top-selling herbal dietary supplement in the food, drug, and mass market channel in the United States in 2005 with over 21 million U.S. dollars in sales.10 At least two studies have assessed the influence of E purpurea root on CYP3A activity in humans.11,12 Using single doses of both oral and iv midazolam as a probe for intestinal and hepatic CYP3A activity, respectively, Gorski et al. observed an 85% increase in the intestinal availability of midazolam (P=0.015) and a 15% reduction in the hepatic availability of the drug (P= 0.006) after 1600 mg (total daily dose) of E purpurea administration for 8 days.11 These data suggest that E purpurea selectively alters the catalytic activity of CYP3A in the liver vs. intestine. Conversely, Gurley et al. found that 28 days of E purpurea whole plant extract administration did not significantly alter CYP3A metabolic serum ratios of 1-hydroxymidazolam:midazolam collected one hr post-dose in 12 healthy volunteers.12 To this end, it is difficult to predict the influence of E purpurea on the pharmacokinetics of CYP3A substrates such as the HIV protease inhibitors. The presence or absence of such interactions may depend on the relative extraction of the coadministered drug by hepatic and intestinal CYP3A. Due to the potentially serious consequences of a drug-drug interaction between E purpurea and HIV protease inhibitors (i.e virologic and/or immunologic failure or drug toxicity) the current study was designed to assess the influence of E purpurea on the steady state pharmacokinetics of Lopinavir Plus Ritonavir in healthy human volunteers.
