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Efavirenz

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https://www.readbyqxmd.com/read/29034770/association-with-polymorphic-marmoset-cytochrome-p450-2c19-of-in-vivo-hepatic-clearances-of-chirally-separated-r-omeprazole-and-s-warfarin-using-individual-marmoset-physiologically-based-pharmacokinetic-models
#1
Takashi Kusama, Akiko Toda, Makiko Shimizu, Shotaro Uehara, Takashi Inoue, Yasuhiro Uno, Masahiro Utoh, Erika Sasaki, Hiroshi Yamazaki
1. Simulated clearances of R-warfarin and efavirenz were recently reported for individual cynomolgus monkeys genotyped for cytochrome P450 2C19 and 2C9, respectively. To expand and verify this modeling procedure, simulations of R/S-omeprazole and R/S-warfarin clearances after oral administrations in individual marmosets were performed using individual simplified physiologically based pharmacokinetic (PBPK) modeling consisting of gut, liver, and central compartments. 2. Pharmacokinetics of R/S-omeprazole were chirally determined using the previously reported plasma microsamples in this study...
October 16, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29033481/adverse-drug-reaction-monitoring-in-patients-on-antiretroviral-therapy-in-a-tertiary-care-hospital-in-eastern-india
#2
Shatavisa Mukherjee, Nikhil Era, Bibhuti Saha, Santanu Kumar Tripathi
BACKGROUND: Besides unparalleled benefits, highly active antiretroviral therapy is also associated with wide range of potential adverse drug reactions (ADRs), which hinders treatment adherence. The present study was thus designed to monitor and explore the pattern of occurrence of ADRs to various antiretroviral therapy (ART) regimens in a tertiary care ART setup. MATERIALS AND METHODS: A prospective, observational clinical study was carried out in the outpatient setting of nodal ART center of Eastern India...
May 2017: Indian Journal of Pharmacology
https://www.readbyqxmd.com/read/29031978/monitoring-the-phase-behavior-of-supersaturated-solutions-of-poorly-water-soluble-drugs-using-fluorescence-techniques
#3
Francesco Tres, Stephen D Hall, Michael A Mohutsky, Lynne S Taylor
Phase transformations of poorly water-soluble drugs, in low concentration, supersaturated aqueous solutions are of considerable interest. Herein, fluorescence lifetime and steady-state fluorescence spectroscopy were employed to investigate the fluorescence properties of the autofluorescent compound, felodipine (a 1,4-dihydropyridine calcium channel blocker), when present as free drug in solution, drug-rich aggregates and crystals. Measurements were also performed in the absence and presence of liver microsomes...
October 11, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29031892/altered-angiogenesis-as-a-common-mechanism-underlying-preterm-birth-small-for-gestational-age-and-stillbirth-in-women-living-with-hiv
#4
Andrea L Conroy, Chloe R Mcdonald, Joel L Gamble, Peter Olwoch, Paul Natureeba, Deborah Cohan, Moses R Kamya, Diane V Havlir, Grant Dorsey, Kevin C Kain
BACKGROUND: Angiogenic processes in the placenta are critical regulators of fetal growth and impact birth outcomes, but there are limited data documenting these processes in HIV-infected women or women from low-resource settings. OBJECTIVE: To determine whether angiogenic factors are associated with adverse birth outcomes in HIV-infected pregnant women started on antiretroviral therapy. STUDY DESIGN: This is a secondary analysis of samples collected as part of a clinical trial randomizing pregnant women infected with HIV to lopinavir/ritonavir (n=166) or efavirenz-based (n=160) antiretroviral therapy in Tororo, Uganda...
October 11, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/29029267/evaluation-of-universal-versus-genotype-guided-efavirenz-dose-reduction-in-pregnant-women-using-population-pharmacokinetic-modelling
#5
Adeniyi Olagunju, Alessandro Schipani, Oluseye Bolaji, Saye Khoo, Andrew Owen
Objectives: Lack of data on the pharmacokinetics of efavirenz in pregnant women at the 400 mg reduced dose currently prevents universal roll-out. Population pharmacokinetic modelling was used to explore pharmacokinetic endpoints at 200, 400 and 600 mg daily doses in pregnant women stratified by CYP2B6 metabolic status. Methods: The analysis was based on 252 plasma efavirenz concentrations from 77 pregnant women (77 sparse, 175 intensive) who received antiretroviral regimens containing 600 mg of efavirenz...
September 26, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29016131/metabolites-from-the-plant-endophytic-fungus-aspergillus-sp-cpcc-400735-and-their-anti-hiv-activities
#6
Xu Pang, Jian-Yuan Zhao, Xiao-Mei Fang, Tao Zhang, De-Wu Zhang, Hong-Yu Liu, Jing Su, Shan Cen, Li-Yan Yu
Thirty-three metabolites including five phenalenone derivatives (1-5), seven cytochalasins (6-12), thirteen butenolides (13-25), and eight phenyl derivatives (26-33) were isolated from Aspergillus sp. CPCC 400735 cultured on rice. The structures of all compounds were elucidated by NMR, MS, and CD experiments, of which 1-5 (asperphenalenones A-E), 6 (aspochalasin R), and 13 (aspulvinone R) were identified as new compounds. Specifically, asperphenalenones A-E (1-5) represent an unusual structure composed of a linear diterpene derivative linked to a phenalenone derivative via a C-C bond...
October 10, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28994660/pharmacokinetics-of-rilpivirine-and-24-week-outcomes-after-switching-from-efavirenz-in-virologically-suppressed-hiv-1-infected-adolescents
#7
Watsamon Jantarabenjakul, Suvaporn Anugulruengkitt, Naruporn Kasipong, Narukjaporn Thammajaruk, Jiratchaya Sophonphan, Torsak Bunupuradah, Tim R Cressey, Angela Colbers, David M Burger, Wanatpreeya Phongsamart, Thanyawee Puthanakit, Chitsanu Pancharoen
BACKGROUND: Rilpivirine (RPV), a non-nucleoside reverse transcriptase inhibitor drug, could be a favorable drug for maintenance therapy in HIV-infected adolescents because it has few long-term side effects. However, data among adolescents switching from efavirenz (EFV) to RPV are limited. This study investigated the pharmacokinetics (PK), safety and efficacy of RPV in virologically-suppressed HIV-1-infected adolescents after switching from EFV. METHODS: Adolescents aged 12-18 years on EFV-based antiretroviral therapy (ART) were switched from EFV to RPV (25 mg, once daily)...
October 10, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28993335/the-effects-of-maraviroc-versus-efavirenz-in-combination-with-zidovudine-lamivudine-on-the-cd4-cd8-ratio-in-treatment-na%C3%A3-ve-hiv-infected-individuals
#8
Sergio Serrano-Villar, Giorgia Caruana, Alexander Zlotnik, José A Pérez-Molina, Santiago Moreno
A low CD4/CD8 ratio during treated HIV infection reflects heightened immune activation and predicts mortality. The effect of different ART regimens on CD4/CD8 ratio recovery remains unclear. We performed a post hoc analysis of the MERIT study, a randomized, double-blind, trial of maraviroc versus efavirenz, in combination with zidovudine-lamivudine, in treatment-naive HIV-infected individuals. We found higher rates of CD4/CD8 ratio normalization with efavirenz, which was driven by greater CD8+ T-cell decline...
October 9, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28992470/the-potential-effects-of-efavirenz-on-oreochromis-mossambicus-after-acute-exposure
#9
L Robson, I E J Barnhoorn, G M Wagenaar
Antiretroviral drugs (ARVs) are hazardous therapeutic pharmaceuticals present in South African surface water. Efavirenz is an ARV commonly used in human immunodeficiency virus (HIV) treatment in South Africa. Although little is known about the toxic effects of efavirenz on fish health, threats of toxicity to the aquatic environment have been reported. Oreochromis mossambicus were exposed under controlled conditions to environmentally-relevant efavirenz concentrations (10.3ng/l) as measured in rivers that flow into the Nandoni Dam in the Vhembe District, South Africa...
October 2, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28991888/commonly-prescribed-antiretroviral-therapy-regimens-and-incidence-of-aids-defining-neurological-conditions
#10
Ellen C Caniglia, Andrew Phillips, Kholoud Porter, Caroline A Sabin, Alan Winston, Roger Logan, John Gill, Marie-Anne Vandenhende, Diana Barger, Sara Lodi, Santiago Moreno, José Ramón Arribas, Antonio Pacheco, Sandra W Cardoso, George Chrysos, Charalabos Gogos, Sophie Abgrall, Dominique Costagliola, Laurence Meyer, Remonie Seng, Ard van Sighem, Peter Reiss, Roberto Muga, Santiago Pérez Hoyos, Dominique Braun, Christoph Hauser, Pilar Barrufet, Maria Leyes, Janet Tate, Amy Justice, Miguel A Hernán
BACKGROUND: The differential effects of commonly prescribed combined antiretroviral therapy (cART) regimens on AIDS-defining neurological conditions (neuroAIDS) remain unknown. SETTING: Prospective cohort studies of HIV-positive individuals from Europe and the Americas included in the HIV-CAUSAL Collaboration. METHODS: Individuals who initiated a first-line cART regimen in 2004 or later containing a nucleoside reverse transcriptase inhibitor (NRTI) backbone and either atazanavir, lopinavir, darunavir, or efavirenz were followed from cART initiation until death, lost to follow-up, pregnancy, the cohort-specific administrative end of follow-up, or the event of interest, whichever occurred earliest...
October 4, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28989077/comparison-of-efficiencies-of-selected-sample-extraction-techniques-for-the-analysis-of-selected-antiretroviral-drugs-in-human-plasma-using-lc-ms
#11
Kwenga Sichilongo, Elliott Mwando, Enoch Sepako, Amos Massele
INTRODUCTION: Sample preparation in bio analytical chemistry poses a challenge because it can be compound dependent. We compared six sample extraction techniques i.e. QuEChERS (Q), liquid extraction (LE), protein precipitation (PPT), Q-PPT, Q-LE and LE-PPT for the extraction of antiretroviral drugs emtricitabine, tenofovir, efavirenz, lopinavir and rotinavir in human blood plasma. METHOD: A multiple reaction monitoring liquid chromatography- tandem mass spectrometry method for the determination of the same antiretroviral drugs developed and validated in this laboratory was used...
October 5, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28986714/comparison-of-antiretroviral-drug-resistance-among-treatment-naive-and-treated-hiv-infected-individuals-in-shiraz-iran
#12
Mohammad Ali Davarpanah, Nasrin Motazedian, Hassan Joulaei, Mohammad Reza Aghasadeghi, Hossein Faramarzi, Ehsan Aghah
The use of anti-retroviral therapy has been effective in controlling the spread of HIV-1, and has prolonged life expectancy, but this success can be affected by the emergence of drug resistance. The main goal of this study was to investigate drug resistance in the reverse transcriptase (RT), and protease (PR) genes among HIV-1 infected individuals. We systematically selected 59 HIV-1 infected individuals from Shiraz Voluntary Counseling and Testing Center (29 treatment- naïve and 30 treated). In this study intravenous drug users older than 18 were included in this study...
October 6, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28986123/possible-anti-depressant-effect-of-efavirenz-and-pro-depressive-like-effect-of-voriconazole-in-specified-doses-in-various-experimental-models-of-depression-in-mice
#13
Tejal K Patel, Vandana B Patel, Digvijay G Rana
BACKGROUND: Reports from experimental and clinical studies have indicated the possible relation between cholesterol and depression. Efavirenz (EFV) and Voriconazole (VRC) have been reported to affect cholesterol-24S-hydroxylase enzyme. The objective of the present study was to evaluate the effect of EFV and VRC in experimental models of depression in mice. METHODS: There was a measurement of immobility time in forced swim test and tail suspension test in which mice were previously subjected to the treatment of EFV (0...
May 1, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28981637/rates-of-virological-suppression-and-drug-resistance-in-adult-hiv-1-positive-patients-attending-primary-healthcare-facilities-in-kwazulu-natal-south-africa
#14
Gillian M Hunt, E Kainne Dokubo, Simbarashe Takuva, Tulio de Oliveira, Johanna Ledwaba, Nomathemba Dube, Pravi Moodley, Jennifer Sabatier, Varough Deyde, Lynn Morris, Elliot Raizes
Background: KwaZulu-Natal (KZN) Province in South Africa has the highest HIV disease burden in the country, with an estimated population prevalence of 24.7%. A pilot sentinel surveillance project was undertaken in KZN to classify the proportion of adult patients failing first-line ART and to describe the patterns of drug resistance mutations (DRMs) in patients with virological failure (VF). Methods: Cross-sectional surveillance of acquired HIV drug resistance was conducted in 15 sentinel ART clinics between August and November 2013...
August 3, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28977086/antiretroviral-changes-during-the-first-year-of-therapy
#15
Antonio Carlos Policarpo Carmo Sá Bandeira, Darcielle Bruna Dias Elias, Malena Gadelha Cavalcante, Denise Girão Limaverde Lima, Lara Gurgel Fernandes Távora
INTRODUCTION: The Brazilian HIV/AIDS management and treatment guideline (PCDT), published in 2013, recommends and standardizes the use of highly active antiretroviral therapy (HAART) in all adult patients, in spite of LTCD4 count. This study aimed to analyze the first year of HAART use in patients from a reference center on HIV/AIDS management in Fortaleza, Ceará. METHOD: This descriptive study reviewed all prescription forms of antiretroviral regimens initiation and changes from January to July 2014...
July 2017: Revista da Associação Médica Brasileira
https://www.readbyqxmd.com/read/28968669/human-immunodeficiency-virus-type-1-drug-resistance-mutations-update
#16
Robert W Shafer
As treatment options coalesce around a smaller number of antiretroviral drugs (ARVs), data are emerging on the drug resistance mutations (DRMs) selected by the most widely used ARVs and on the impact of these DRMs on ARV susceptibility and virological response to first- and later-line treatment regimens. Recent studies have described the DRMs that emerge in patients receiving tenofovir prodrugs, the nonnucleoside reverse transcriptase inhibitors efavirenz and rilpivirine, ritonavir-boosted lopinavir, and the integrase inhibitors raltegravir and elvitegravir...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28961972/hiv-pretreatment-drug-resistance-trends-in-three-geographic-areas-of-mexico
#17
Claudia García-Morales, Daniela Tapia-Trejo, Verónica S Quiroz-Morales, Samuel Navarro-Álvarez, Carlos A Barrera-Arellano, Jesús Casillas-Rodríguez, Karla A Romero-Mora, María Gómez-Palacio-Schjetnan, Akio Murakami-Ogasawara, Santiago Ávila-Ríos, Gustavo Reyes-Terán
Background: Pretreatment drug resistance (PDR) levels to NNRTI approaching 10% have recently been reported in Mexico. However, subnational differences may exist in PDR prevalence and transmission dynamics. Objectives: : We longitudinally assessed HIV PDR in three geographic areas of Mexico. Patients and methods: HIV-infected, antiretroviral-naive individuals were recruited from 2008 to 2016, from the Central Metropolitan Zone (CMZ), Cancun and Tijuana (1194, 773 and 668 respectively)...
August 23, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28961719/impact-of-baseline-plasma-hiv-1-rna-and-time-to-virological-suppression-on-virological-rebound-according-to-first-line-antiretroviral-regimen
#18
François Raffi, Matthieu Hanf, Tristan Ferry, Lydie Khatchatourian, Véronique Joly, Pascal Pugliese, Christine Katlama, Olivier Robineau, Catherine Chirouze, Christine Jacomet, Pierre Delobel, Isabelle Poizot-Martin, Isabelle Ravaux, Claudine Duvivier, Amandine Gagneux-Bugnon, David Rey, Jacques Reynes, Thierry May, Firouzé Bani-Sadr, Bruno Hoen, Marine Morrier, André Cabie, Clotilde Allavena
Objectives: We investigated the risk of virological rebound in HIV-1-infected patients achieving virological suppression on first-line combined ART (cART) according to baseline HIV-1 RNA, time to virological suppression and type of regimen. Patients and methods: Subjects were 10 836 adults who initiated first-line cART (two nucleoside or nucleotide reverse transcriptase inhibitors + efavirenz, a ritonavir-boosted protease inhibitor or an integrase inhibitor) from 1 January 2007 to 31 December 2014...
September 6, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28960269/variants-in-the-cyp2b6-3-utr-alter-in-vitro-and-in-vivo-cyp2b6-activity-potential-role-of-micrornas
#19
Kimberly S Burgess, Joseph Ipe, Marelize Swart, Ingrid F Metzger, Jessica Lu, Brandon T Gufford, Nancy Thong, Zeruesenay Desta, Roger Gaedigk, Robin Pearce, Andrea Gaedigk, Yunlong Liu, Todd C Skaar
CYP2B6*6 and CYP2B6*18 are the most clinically important variants causing reduced CYP2B6 protein expression and activity. However, these variants do not account for all variability in CYP2B6 activity. Emerging evidence has shown that genetic variants in the 3'UTR may explain variable drug response by altering microRNA regulation. Five 3'UTR variants were associated with significantly altered efavirenz AUC0-48 (8-OH-EFV/EFV) ratios in healthy human volunteers. The rs70950385 (AG>CA) variant, predicted to create a microRNA binding site for miR-1275, was associated with 33% decreased CYP2B6 activity among normal metabolizers (AG/AG vs...
September 27, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28953037/a-comparison-of-dried-blood-spots-versus-conventional-plasma-collection-for-the-characterisation-of-efavirenz-pharmacokinetics-in-a-large-scale-global-clinical-trial-the-encore1-study
#20
Alieu B Amara, Laura J Else, Dianne Carey, Saye Khoo, David J Back, Janaki Amin, Sean Emery, Rebekah L Puls
BACKGROUND: The aim of this study was to determine the utility of dried blood spots (DBS) compared with conventional plasma collection methods for characterisation of efavirenz pharmacokinetics, in the setting of a large-scale, global clinical trial (ENCORE1). METHODS: 630 patients were recruited from 38 sites and had single matched whole blood DBS and plasma samples (mid-dose interval) taken at weeks 4 and 12 of treatment. In addition, a sub-group of patients underwent intensive DBS and plasma sampling (0-24 hours) to provide full profile data for pharmacokinetic parameters...
September 22, 2017: Therapeutic Drug Monitoring
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