atazanavir

Intestinal drug solubility is a key parameter controlling absorption after the administration of a solid oral dosage form. The ability to measure fed state solubility in vitro is limited and multiple simulated intestinal fluid recipes have been developed but with no consensus which is optimal. This study has utilised nine bioequivalent simulated fed intestinal media recipes that cover over 90% of the compositional variability of sampled fed human intestinal fluid. The solubility of 24 drugs (Acidic; furosemide, ibuprofen, indomethacin, mefenamic acid, naproxen, phenytoin, piroxicam, valsartan, zafirlukast: Basic; aprepitant, atazanavir, bromocriptine, carvedilol, dipyridamole, posaconazole, tadalafil: Neutral; acyclovir, carbamazepine, felodipine, fenofibrate, griseofulvin, itraconazole, paracetamol, probucol) has been assessed to determine if structured solubility behaviour is present...

Vericiguat (Verquvo; US: Merck, other countries: Bayer) is a novel drug for the treatment of chronic heart failure. Preclinical studies have demonstrated that the primary route of metabolism for vericiguat is glucuronidation, mainly catalyzed by uridine diphosphate-glucuronosyltransferase (UGT)1A9 and to a lesser extent UGT1A1. Whereas a drug-drug interaction (DDI) study of the UGT1A9 inhibitor mefenamic acid showed a 20% exposure increase, the effect of UGT1A1 inhibitors has not been assessed clinically. This modeling study describes a physiologically-based pharmacokinetic (PBPK) approach to complement the clinical DDI liability assessment and support prescription labeling...

Lamin A/C is a well-established key contributor to nuclear stiffness and its role in nucleus mechanical properties has been extensively studied. However, its impact on whole-cell mechanics has been poorly addressed, particularly concerning measurable physical parameters. In this study, we combined microfluidic experiments with theoretical analyses to quantitatively estimate the whole-cell mechanical properties. This allowed us to characterize the mechanical changes induced in cells by lamin A/C alterations and prelamin A accumulation resulting from atazanavir treatment or lipodystrophy-associated LMNA R482W pathogenic variant...

Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/ AIDS) and unplanned pregnancy affect female reproductive health globally. A single product providing a dual purpose of contraception and HIV prophylaxis may improve adherence to the therapy. Thus, we formulated a female-centric multipurpose prevention technology (MPT) comprising of nanoparticle loaded vaginal gel formulation acting as a contraceptive and microbicide. Eudragit® S100 nanoparticles of Atazanavir sulphate (ATZ; antiviral) and Fluoxetine hydrochloride (FLX; repurposed spermicide) were prepared for pH dependent drug release and loaded in carrageenan and HPMC K200M gel...

Bilirubin is excreted into the bile from hepatocytes, mainly as monoglucuronosyl and bisglucuronosyl conjugates, reflecting bilirubin glucuronidation activity. However, there is limited information on the in vitro evaluation of liver cell lines or primary hepatocytes. This study aimed to investigate variations in the bilirubin metabolic function of canine and human hepatocyte spheroids formed in a three-dimensional (3D) culture system indicated by the formation of bilirubin glucuronides when protease inhibitors such as atazanavir, indinavir, ritonavir, and nelfinavir were treated with bilirubin...

BACKGROUND: Coronavirus disease 2019 (COVID-19) has demonstrated several clinical manifestations which include not only respiratory system issues but also liver, kidney, and other organ injuries. One of these abnormalities is coagulopathies, including thrombosis and disseminated intravascular coagulation. Because of this, the administration of low molecular weight heparin is required for patients that need to be hospitalized. In addition, Remdesivir is an antiviral that was used against Middle East Acute Respiratory Syndrome, Ebola, Acute Respiratory Syndrome, and other diseases, showing satisfactory results on recovery...

Disproportionation is a major issue in formulations containing salts of weakly basic drugs. Despite considerable interest in risk assessment approaches for disproportionation, the prediction of salt-to-base conversion remains challenging. Recent studies have highlighted several confounding factors other than pHmax that appear to play an important role in salt disproportionation and have suggested that kinetic barriers need to be considered in addition to the thermodynamic driving force when assessing the risk of a salt to undergo conversion to parent free base...

A highly sensitive LC-MS/MS methods were developed and validated to quantify nine antiretrovirals (atazanavir [ATV], tenofovir [TFV], emtricitabine [FTC], darunavir [DRV], dolutegravir [DTG], efavirenz [EFV], lamivudine [3TC], raltegravir [RAL], and ritonavir [RTV]) in human cerebral spinal fluid (CSF). The approach remedies adsorption issues caused by polypropylene based sample collection tubes. 1% ammonium hydroxide in methanol was added in an amount equal to the volume of each quality control (QC) or patient sample...

Viruses cause a variety of diseases in the human body. Antiviral agents are used to prevent the production of disease-causing viruses. These agents obstruct and kill the virus's translation and replication. Because viruses share the metabolic processes of the majority of host cells, finding targeted medicines for the virus is difficult. In the ongoing search for better antiviral agents, the USFDA approved EVOTAZ, a new drug discovered for the treatment of Human Immunodeficiency Virus (HIV). It is a once-daily (OD) fixed-dose combination of Cobicistat, a cytochrome P450 (CYP) enzyme inhibitor, and Atazanavir, a protease inhibitor...

A novel sericin-dextran conjugate (SDC) and self-assembled microparticles has been prepared for improving solubility of atazanavir. Microparticles of SDC were assembled by the reprecipitation method. The size and morphology of SDC microparticles could be adjusted by the concentration and solvents. Low concentration was conducive to the preparation of microspheres. Heterogeneous microspheres could be prepared in ethanol with the range of 85-390 nm, and hollow mesoporous microspheres in propanol with an average particle size of 2...

Aim: The current research focused on formulation of spherical crystal agglomerates (SCA) of atazanavir sulphate for improving flow property and solubility. Materials & methods: SCA were formulated by quasi-emulsification solvent diffusion. Methanol, water and dichloromethane were employed as a good solvent, bad solvent and bridging liquid respectively. Results & conclusion: SCA with improved solubility and micromeritic properties were directly compressed into a tablet. The SCA tablets had higher dissolution rates compared with plain drug and marketed product...

BACKGROUND AND OBJECTIVES: Obesity trends and metabolic dysregulation are rising in people living with HIV using antiretrovirals (ARVs). Underlying causes and preventive strategies are being investigated. Two glucagon like-peptide 1 (GLP-1) agonists, liraglutide and semaglutide, were formerly approved as glucose-lowering drugs and have been recently approved for long-term weight loss in people with obesity. Due to the lack of therapeutic guidelines or clinical trials in people with HIV, we discuss the potential benefits, safety aspects and pharmacological considerations of prescribing liraglutide and semaglutide in people with HIV...

BACKGROUND: We evaluated the pharmacokinetics of tenofovir alafenamide fumarate (TAF) and tenofovir in a subset of African children enrolled in the CHAPAS-4 trial. METHODS: Children aged 3-15 years with human immunodeficiency virus infection failing first-line antiretroviral therapy were randomized to emtricitabine/TAF versus standard-of-care nucleoside reverse transcriptase inhibitor combination, plus dolutegravir, atazanavir/ritonavir, darunavir/ritonavir, or lopinavir/ritonavir...

OBJECTIVES: Data are lacking on the virologic efficacy and durability of modern antiretroviral treatment (ART) regimens during pregnancy. We compared virologic outcomes at delivery among women receiving dolutegravir versus other ART and the rate of change of the initial pregnancy regimen. DESIGN: Single site retrospective cohort between 2009-2019. METHODS: We used univariable and multivariable generalized estimating equations to model the relationship between the maternal ART anchor and the proportion of women with a viral load ≥20 HIV RNA copies/mL of plasma closest to delivery (suboptimal virologic control) and with a viral load ≥20 copies/mL at any time in the third trimester...

OBJECTIVE: Inflammation-induced free radical release is important in the pathogenesis of several diseases, including atherosclerosis and sepsis. Heme oxygenase (HO) breaks down heme into carbon monoxide, iron, and biliverdin. Biliverdin IXα is directly converted to bilirubin by biliverdin reductase. Unconjugated bilirubin is a powerful antioxidant, and elevated levels have beneficial effects in preclinical models and human cardiovascular disease. However, its impact during acute inflammation in humans is unknown...

Viruses belong to the class of micro-organisms that are well known for causing infections in the human body. Antiviral medications are given out to prevent the spread of disease-causing viruses. When the viruses are actively reproducing, these agents have their greatest impact. It is particularly challenging to develop virus-specific medications since viruses share the majority of the metabolic functions of the host cell. In the continuous search for better antiviral agents, the United States Food and Drug Administration (USFDA) approved a new drug named Evotaz on January 29, 2015 for the treatment of human immunodeficiency virus (HIV)...

Tenofovir (TFV) and emtricitabine (FTC) are part of the recommended highly active antiretroviral therapy (ART). Both molecules show a large interindividual pharmacokinetic (PK) variability. Here, we modeled the concentrations of plasma TFV and FTC and their intracellular metabolites (TFV diphosphate [TFV-DP] and FTC triphosphate [FTC-TP]) collected after 4 and 24 weeks of treatment in 34 patients from the ANRS 134-COPHAR 3 trial. These patients received daily (QD) atazanavir (300 mg), ritonavir (100 mg), and a fixed-dose combination of coformulated TFV disoproxil fumarate (300 mg) and FTC (200 mg)...

Candida auris represents an urgent health threat. Here, we identified atazanavir as a potent drug capable of resensitizing C. auris clinical isolates to the activity of azole antifungals. Atazanavir was able to significantly inhibit the efflux pumps, glucose transport, and ATP synthesis of all tested isolates of C. auris. In addition, the combination of itraconazole with atazanavir-ritonavir significantly reduced the burden of azole-resistant C. auris in murine kidneys by 1.3 log10 (95%), compared to itraconazole alone...

BACKGROUND: Delayed puberty is a recognized phenomenon among children living with HIV type 1 infection but has not been widely reported among adolescents on second-line or newer treatments in high burden settings. The study aimed to determine the prevalence of, and factors associated with delayed puberty among adolescents on boosted protease inhibitor-based second-line antiretroviral therapy (ART) in Uganda. METHODS: Between December 2017 and May 2018, we conducted a cross-sectional study among adolescents living with HIV (ALWHIV) 10-19 years of age on atazanavir- and lopinavir-based regimens at the Paediatric Infectious Diseases Clinic, Kampala...

A HIV-infected female treated with a combination of emtricitabine/elvitegravir/tenofovir since 2017 presented an acute renal failure during her hospitalization for a SARS-CoV2 pneumonia. A computed tomography demonstrated left ureterohydronephrosis and ureteral stone. Fragments extracted by ureteroscopy showed a calculus composed of atazanavir and calcium oxalate. The patient's medical history showed atazanavir intake during ten years and then discontinued in 2017. This case report emphasizes that drug-induced urolithiasis should be considered when renal function declines, even far from discontinuation of atazanavir and without clinical signs of renal colitis...