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Hiv and pharmacokinetics

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https://www.readbyqxmd.com/read/28317117/comparative-pharmacokinetic-evaluation-of-lopinavir-and-lopinavir-loaded-solid-lipid-nanoparticles-in-hepatic-impaired-rat-model
#1
Punna Rao Ravi, Rahul Vats
OBJECTIVE: Drug-induced hepatotoxicity is a major cause of concern in patients receiving HIV/TB co-treatment. Lopinavir (LPV), an anti-HIV drug, shows poor plasma exposure due to hepatic first-pass metabolism. In this study, we investigated the effect of hepatotoxicity on pharmacokinetics of free LPV and LPV-loaded solid lipid nanoparticles (LPV SLNs) in male Wistar rats. METHODS: Hepatic impairment model in rats was developed by injecting CCl4 (i.p., 2 ml/kg). Comparative pharmacokinetic (n = 5) and tissue distribution studies (n = 3) were conducted following oral administration (20 mg/kg) of free LPV and LPV SLNs in normal and hepatic impaired rats...
March 19, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28296019/health-care-provider-communication-training-in-rural-tanzania-empowers-hiv-infected-patients-on-antiretroviral-therapy-to-discuss-adherence-problems
#2
S Erb, E Letang, T R Glass, A Natamatungiro, D Mnzava, H Mapesi, M Haschke, U Duthaler, B Berger, L Muri, J Bader, C Marzolini, L Elzi, T Klimkait, W Langewitz, M Battegay
OBJECTIVES: Self-reported adherence assessment in HIV-infected patients on antiretroviral therapy (ART) is challenging and may overestimate adherence. The aim of this study was to improve the ability of health care providers to elicit patients' reports of nonadherence using a "patient-centred" approach in a rural sub-Saharan African setting. METHODS: A prospective interventional cohort study of HIV-infected patients on ART for ≥ 6 months attending an HIV clinic in rural Tanzania was carried out...
March 13, 2017: HIV Medicine
https://www.readbyqxmd.com/read/28293270/effect-of-moringa-oleifera-lam-leaf-powder-on-the-pharmacokinetics-of-nevirapine-in-hiv-infected-adults-a-one-sequence-cross-over-study
#3
Tsitsi G Monera-Penduka, Charles C Maponga, Alan R Wolfe, Lubbe Wiesner, Gene D Morse, Charles F B Nhachi
BACKGROUND: Moringa oleifera Lam., an herb commonly consumed by HIV-infected people on antiretroviral therapy, inhibits cytochrome P450 3A4, 1A2 and 2D6 activity in vitro; and may alter the pharmacokinetics (PK) of antiretroviral drugs metabolized via the same pathways. However, in vitro drug interaction activity may not translate to a clinically significant effect. Therefore, the effect of moringa leaf powder on the PK of nevirapine in HIV-infected people was investigated. METHODS: Adult patients at steady-state dosing with nevirapine were admitted for 12-h intensive PK sampling following a 21-day herbal medicine washout...
2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28288665/effect-of-moringa-oleifera-lam-leaf-powder-on-the-pharmacokinetics-of-nevirapine-in-hiv-infected-adults-a-one-sequence-cross-over-study
#4
Tsitsi G Monera-Penduka, Charles C Maponga, Alan R Wolfe, Lubbe Wiesner, Gene D Morse, Charles F B Nhachi
BACKGROUND: Moringa oleifera Lam., an herb commonly consumed by HIV-infected people on antiretroviral therapy, inhibits cytochrome P450 3A4, 1A2 and 2D6 activity in vitro; and may alter the pharmacokinetics (PK) of antiretroviral drugs metabolized via the same pathways. However, in vitro drug interaction activity may not translate to a clinically significant effect. Therefore, the effect of moringa leaf powder on the PK of nevirapine in HIV-infected people was investigated. METHODS: Adult patients at steady-state dosing with nevirapine were admitted for 12-h intensive PK sampling following a 21-day herbal medicine washout...
March 14, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28287204/-biliary-and-kidney-lithiasis-during-treatment-with-daclatasvir-sofosbuvir-ribavirin-and-atazanavir-ritonavir-abacavir-lamivudine-in-an-hiv-hcv-genotype-4-infected-patient-a-case-report
#5
Andrea Vavassori, Paola Lanza, Ilaria Izzo, Salvatore Casari, Silvia Odolini, Serena Zaltron, Elena Festa, Francesco Castelli
New Direct-acting Antiviral Agents (DAA)-based anti-HCV therapies currently provide extraordinary opportunities to cure patients. Drug-drug interactions are however a real challenge during treatment. In particular, in HIV-infected patients in cART, DAA choice is limited by such interactions, which can result both in reduced efficacy and toxicity. We report the case of a HIV-infected patient on cART with atazanavir/ritonavir/abacavir/lamivudine, who presented kidney and biliary lithiasis, the latter treated with endoscopic retrograde cholangiopancreatography and endoscopic biliary sphincterotomy, after beginning anti-HCV treatment with daclatasvir/sofosbuvir/ribavirin...
February 2017: Recenti Progressi in Medicina
https://www.readbyqxmd.com/read/28285916/discovery-and-optimization-of-2-pyridinone-aminal-integrase-strand-transfer-inhibitors-for-the-treatment-of-hiv
#6
John D Schreier, Mark W Embrey, Izzat T Raheem, Guillaume Barbe, Louis-Charles Campeau, David Dubost, Jamie McCabe Dunn, Jay Grobler, Timothy J Hartingh, Daria J Hazuda, Daniel Klein, Michael D Miller, Keith P Moore, Natalie Nguyen, Natasa Pajkovic, David A Powell, Vanessa Rada, John M Sanders, John Sisko, Thomas G Steele, John Wai, Abbas Walji, Min Xu, Paul J Coleman
HIV integrase strand transfer inhibitors (InSTIs) represent an important class of antiviral therapeutics with proven efficacy and excellent tolerability for the treatment of HIV infections. In 2007, Raltegravir became the first marketed strand transfer inhibitor pioneering the way to a first-line therapy for treatment-naïve patients. Challenges with this class of therapeutics remain, including frequency of the dosing regimen and the genetic barrier to resistance. To address these issues, research towards next-generation integrase inhibitors has focused on imparting potency against RAL-resistent mutants and improving pharmacokinetic profiles...
February 20, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28273373/acute-care-management-of-the-hiv-infected-patient-a-report-from-the-hiv-practice-and-research-network-of-the-american-college-of-clinical-pharmacy
#7
Spencer H Durham, Melissa E Badowski, Michelle D Liedtke, R Chris Rathbun, Patricia Pecora Fulco
OBJECTIVE: HIV-infected patients admitted to the hospital have complex antiretroviral therapy (ART) regimens with an increased medication error rate upon admission. This report is intended to provide a resource for clinicians managing HIV-infected patients and ART in the inpatient setting. METHODS: A survey of the authors was conducted to evaluate common issues that arise during an acute hospitalization for HIV-infected patients. After a group consensus, a review of the medical literature was performed to determine the supporting evidence for the following HIV associated hospital queries: admission/discharge orders, antiretroviral hospital formularies, laboratory monitoring, altered hepatic/renal function, drug-drug interactions (DDIs), enteral administration, and therapeutic drug monitoring...
March 8, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28263467/mechanisms-and-consequences-of-drug-drug-interactions
#8
David J Greenblatt
Medications used to treat human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections present a special challenge with respect to the management of potential and actual drug-drug interactions (DDIs). The HIV and HCV treatments may interact with each other, and also interact with drugs of abuse and/or with medications used to treat substance abuse. Possible mechanisms of these DDIs generally include induction or inhibition of activity/expression of human cytochromes P450, glucuronosyl transferases, or energy-dependent transport proteins...
March 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28263461/current-concepts-in-methadone-metabolism-and-transport
#9
Evan D Kharasch
Methadone is a cornerstone therapy for opioid addiction and a public health strategy for HIV/AIDS and hepatitis C reduction. Methadone is also used for acute and chronic pain. As use for chronic pain has grown, so too have adverse events. Constitutive and acquired (drug interactions) inter- and intraindividual variability in methadone pharmacokinetics and pharmacodynamics confounds reliable clinical use. Identification of enzymes and transporters responsible for methadone disposition has been a long-sought ideal...
March 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28263456/drug-drug-interactions-and-diagnostics-for-drug-users-with-hiv-and-hiv-hcv-coinfections-introduction
#10
Jag H Khalsa, Andrew H Talal, Gene Morse
Substance use and pharmacologic treatment of co-occurring infections such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV) are associated with many adverse consequences including pharmacokinetic and pharmacodynamic drug-drug interactions (DDIs). The National Institute on Drug Abuse sponsored a 2-day conference on DDIs at which clinicians/scientists from government, academia, and the pharmaceutical industry presented the most current research findings to formulate a comprehensive overview of DDIs...
March 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28243600/systematic-approach-for-the-formulation-and-optimization-of-solid-lipid-nanoparticles-of-efavirenz-by-high-pressure-homogenization-using-design-of-experiments-for-brain-targeting-and-enhanced-bioavailability
#11
Shweta Gupta, Rajesh Kesarla, Narendra Chotai, Ambikanandan Misra, Abdelwahab Omri
The nonnucleoside reverse transcriptase inhibitors, used for the treatment of HIV infections, are reported to have low bioavailability pertaining to high first-pass metabolism, high protein binding, and enzymatic metabolism. They also show low permeability across blood brain barrier. The CNS is reported to be the most important HIV reservoir site. In the present study, solid lipid nanoparticles of efavirenz were prepared with the objective of providing increased permeability and protection of drug due to biocompatible lipidic content and nanoscale size and thus developing formulation having potential for enhanced bioavailability and brain targeting...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28231276/alterations-in-cellular-pharmacokinetics-and-pharmacodynamics-of-elvitegravir-in-response-to-ethanol-exposure-in-hiv-1-infected-monocytic-u1-cells
#12
Narasimha M Midde, Namita Sinha, Pradeep B Lukka, Bernd Meibohm, Santosh Kumar
Ethanol consumption is negatively associated with antiretroviral therapy (ART) adherence and general health in HIV positive individuals. Previously, we demonstrated ethanol-mediated alterations to metabolism of elvitegravir (EVG) in human liver microsomes. In the current study, we investigated ethanol influence on the pharmacokinetic and pharmacodynamic interactions of EVG in HIV infected monocytic (U1) cells. U1 cells were treated with 5 μM EVG, 2 μM Cobicistat (COBI), a booster drug, and 20 mM ethanol for up to 24 hours...
2017: PloS One
https://www.readbyqxmd.com/read/28219799/uplc-ms-ms-method-for-the-simultaneous-quantification-of-three-new-antiretroviral-drugs-dolutegravir-elvitegravir-and-rilpivirine-and-other-thirteen-antiretroviral-agents-plus-cobicistat-and-ritonavir-boosters-in-human-plasma
#13
Marco Simiele, Alessandra Ariaudo, Amedeo De Nicolò, Fabio Favata, Martina Ferrante, Chiara Carcieri, Stefano Bonora, Giovanni Di Perri, Antonio De Avolio
Rilpivirine (RPV), dolutegravir (DTG) and elvitegravir (EVG) are the latest antiretroviral drugs approved for treatment of HIV infection. Currently, poor information is currently available concerning their pharmacokinetic and pharmacodynamic properties, thus making the use of therapeutic drug monitoring for these drugs not useful. This lack of information is partially due to the absence of an high-throughput method for their simultaneous quantification together with other antiretroviral drugs. In this work, we describe the development and validation of a new UPLC-MS/MS method to quantify these drugs, together with other fourteen antiretroviral agents, in human plasma...
February 3, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28206979/effect-of-gender-and-age-on-the-relative-bioavailability-of-doravirine-results-of-a-phase-i-trial-in-healthy-subjects
#14
Martin O Behm, Ka L Yee, Li Fan, Paul Fackler
BACKGROUND: Doravirine is a potent, once-daily, non-nucleoside reverse transcriptase inhibitor with a distinct resistance profile in Phase 3 development for the treatment of HIV-1. As doravirine may be administered to women and the elderly, we investigated the impact of gender and age in doravirine pharmacokinetics. METHODS: In this Phase 1, open-label, single-period, parallel-group investigation, doravirine 100 mg was administered to 36 healthy subjects in 3 groups: elderly men (n=12, 65-80 years), elderly women (n=12, 65-80 years), and young women (n=12, 18-50 years)...
February 16, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28198203/enteral-administration-of-twice-daily-dolutegravir-and-rilpivirine-as-a-part-of-a-triple-therapy-regimen-in-a-critically-ill-patient-with-hiv
#15
Sarah Lynn Turley, Patricia Pecora Fulco
The administration of antiretroviral therapy (ART) in intubated critically ill patients may be challenging. Limited pharmacokinetic data exist characterizing the effects of crushed ART with subsequent enteral administration on antiretroviral drug concentrations or the clinical impact on HIV virologic suppression. We report a case of a 27-year-old HIV-positive male with presumed multidrug-resistant HIV and a diagnosis of lymphoma who required enteral ART administration after intensive care unit admission. Crushed twice-daily dolutegravir (separated from enteral nutrition by 2 hours) and rilpivirine (concurrently with a bolus feed) were administered via an orogastric tube...
January 1, 2017: Journal of the International Association of Providers of AIDS Care
https://www.readbyqxmd.com/read/28196003/antiviral-activity-safety-and-pharmacokinetics-of-bictegravir-as-10-day-monotherapy-in-hiv-1-infected-adults
#16
Joel E Gallant, Melanie Thompson, Edwin DeJesus, Gene W Voskuhl, Xuelian Wei, Heather Zhang, Kirsten White, Andrew Cheng, Erin Quirk, Hal Martin
OBJECTIVE: to evaluate antiviral activity, safety, and pharmacokinetics of short-term monotherapy with bictegravir (bic), a novel, potent hiv integrase strand-transfer inhibitor (insti) DESIGN:: Phase 1b, randomized, double-blinded, adaptive, sequential cohort, placebo-controlled study METHODS:: HIV-infected adults not taking antiretroviral therapy were randomized to receive BIC (5, 25, 50, or 100 mg) or placebo once daily for 10 days. Primary endpoint was time-weighted average change from baseline to Day 11 (DAVG11) for plasma HIV-1 RNA...
February 8, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28193650/interaction-of-rifampicin-and-darunavir-ritonavir-or-darunavir-cobicistat-in-vitro
#17
Owain Roberts, Saye Khoo, Andrew Owen, Marco Siccardi
Treatment of HIV patients co-infected with tuberculosis (TB) is challenging due to drug-drug interactions (DDIs) between antiretrovirals (ARVs) and anti-TB drugs. The aim of this study was to quantify the effects of cobicistat (COBI), or ritonavir (RTV), in modulating DDIs between darunavir (DRV) and rifampicin (RIF) in a human hepatocyte-based in vitro model. Human primary hepatocyte cultures were incubated with RIF alone, or in combination with either COBI or RTV for three days, followed by co-incubation with DRV for one hour...
February 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28188763/hiv-antiretroviral-drug-efavirenz-induces-anxiety-like-and-depression-like-behavior-in-rats-evaluation-of-neurotransmitter-alterations-in-the-striatum
#18
Giuliana Ignácio Teixeira Cavalcante, Adriano José Maia Chaves Filho, Maria Isabel Linhares, Camila Nayane de Carvalho Lima, Edith Teles Venâncio, Emiliano Ricardo Vasconcelos Rios, Francisca Cléa Florenço de Souza, Silvânia Maria Mendes Vasconcelos, Danielle Macêdo, Marta Maria de França Fonteles
Efavirenz (EFV) is an effective antiretroviral drug with a favorable pharmacokinetic profile and widely used in combination regimens to treat HIV infection. However, there are major concerns about the safety of this drug. Patients treated with EFV often experience neuropsychiatric adverse effects, which frequently lead to switching to alternative EFV-free regimens. The mechanisms involved in the central action of EFV are intrinsically unclear. Thus, this study aimed to investigate the effects of acute and subchronic (2 weeks) EFV administration in a series of behavioral tests for anxiety-like and depression-like behavior in healthy rats...
February 7, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28187506/the-effect-of-gene-variants-on-levonorgestrel-pharmacokinetics-when-combined-with-antiretroviral-therapy-containing-efavirenz-or-nevirapine
#19
M Neary, M Lamorde, A Olagunju, K M Darin, C Merry, P Byakika-Kibwika, D J Back, M Siccardi, A Owen, K K Scarsi
Reduced levonorgestrel concentrations from the levonorgestrel contraceptive implant was previously seen when given concomitantly with efavirenz. We sought to assess whether single nucleotide polymorphisms (SNPs) in genes involved in efavirenz and nevirapine metabolism were linked to these changes in levonorgestrel concentration. SNPs in CYP2B6, CYP2A6, NR1I2 and NR1I3 were analysed. Associations of participant demographics and genotype with levonorgestrel pharmacokinetics were evaluated in HIV-positive women using the levonorgestrel implant plus efavirenz- or nevirapine-based ART, in comparison to ART-naïve women using multivariate linear regression...
February 10, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28182610/pharmacokinetics-and-safety-of-darunavir-ritonavir-in-hiv-infected-pregnant-women
#20
REVIEW
Saye Khoo, Gilles Peytavin, David Burger, Andrew Hill, Kimberley Brown, Christiane Moecklinghoff, Charles La Porte, Maria Blanca Hadacek
The dosage of darunavir/ritonavir is 800/100 mg once daily for treatment-naive patients or treatment-experienced patients with no prior darunavir resistance associated mutations, and 600/100 mg twice daily for treatment-experienced patients with one or more darunavir resistance associated mutations. Results from the five available pharmacokinetic studies show reductions in total darunavir plasma concentrations of between 20-50% during the third trimester of pregnancy. The unbound darunavir concentrations have been measured only in subsets of patients in two of the five pharmacokinetic studies...
January 2017: AIDS Reviews
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