Clinical Pharmacology in HIV Therapy

Atta, Mohamed G.; Seigneux, Sophie de; Lucas, Gregory M.

doi:10.2215/cjn.02240218

Cited by 81 publications

(69 citation statements)

References 63 publications

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“…Our data are in accordance with registries of adverse-drug reactions in HIV-infected patients suggesting null or minimal toxicity for T20 or RAL [4]. Moreover, a recent review confirms the safety profile of RAL [44].…”

Section: Discussionsupporting

confidence: 91%

“…A combination of two nucleoside reverse transcriptase inhibitors (NRTIs) plus either a boosted protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI) has constituted the standard highly active antiretroviral treatment (HAART) for many years [1][2][3][4]. Despite harbouring validated therapeutic efficacy, some of these drugs as the virus itself have been associated with early metabolic, mitochondrial, renal and hepatic toxicity that may induce late organ-specific diseases including hyperlipidaemia, hyperlactatemia, insulin resistance and lipoatrophy [4][5][6][7][8][9][10][11].These alterations may result in an increased risk for cardiovascular disease, together with renal or hepatic disease [5,7,10,12]. Adverse clinical effects of PIs, NRTIs and NNRTIs have been associated with secondary interactions of these drugs with molecular pathways essential for cell function.…”

Section: Introductionmentioning

confidence: 99%

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Metabolic, mitochondrial, renal and hepatic safety of enfuvirtide and raltegravir antiretroviral administration: Randomized crossover clinical trial in healthy volunteers

et al. 2019

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Context Classical antiretroviral agents may acutely impact on metabolic, mitochondrial, renal and hepatic function in HIV-infected and uninfected persons. Fusion and integrase inhibitors are supposed to be safer, but have been scarcely investigated. To avoid any interference with HIV or other antiretrovirals, we assessed markers of these toxicities in healthy adult volunteers treated with Enfuvirtide (T20) or Raltegravir (RAL). Methods Twenty-six healthy participants were randomized to T20/90mg vs. placebo (n = 12) or RAL/ 400mg vs. placebo (n = 14) every 12h in two 7-day periods separated by a 4-week washout period. Major end-points were changes in lipid profile (total cholesterol, high-density-lipoprotein (HDL)-cholesterol, low-density-lipoprotein (LDL)-cholesterol, triglycerides), insulin resistance (glucose) and mitochondrial toxicity (mitochondrial DNA content-mtDNA-in peripheral blood mononuclear cells). Renal and hepatic toxicity (creatinine, alanine transaminase (AST), alanine aminotransferase (ALT), bilirubin and total plasma proteins) and overall safety were also analysed. Effect of period, treatment, and basal measures were evaluated for each end-point. Results Neither T20-administration nor RAL-administration yielded to any statistic significant change in the markers of metabolic, mitochondrial, renal or hepatic toxicity assessed. No symptoms indicative of drug toxicity were neither found in any subject.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Metabolic, mitochondrial, renal and hepatic safety of enfuvirtide and raltegravir antiretroviral administration: Randomized crossover clinical trial in healthy volunteers

et al. 2019

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“…Figure 18: Diary of key sentinel timeline events from discovery to evolution of therapy of HIV-1. AZT, Zidovudine [348]. Ever since the first report by the New York Times on a mysterious illness in 1981 and the identification of HIV-1 as the cause of this illness in 1983, significant strides have been made in the treatment and management of HIV-1.…”

Section: Hiv/aidsmentioning

confidence: 99%

Clinical Pharmacists in Chronic Care

Mohiuddin¹

2019

GJMR

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Pharmacy practice has changed significantly lately. The professionals have the chance to contribute straightforwardly to patient consideration so as to lessen morbimortality identified with medication use, promoting wellbeing and preventing diseases. Healthcare organizations worldwide are under substantial pressure from increasing patient demand. Unfortunately, a cure is not always possible particularly in this era of chronic complications, and the role of physicians has become limited to controlling and palliating symptoms.The increasing population of patients with longterm conditions are associated with high levels of morbidity, healthcare costs and GP workloads. Clinical pharmacy took over an aspect of medical care that had been partially abandoned by physicians. Overburdened by patient loads and the explosion of new drugs, physicians turned to pharmacists more and more for drug information, especially within institutional settings. Once relegated to counting and pouring, pharmacists headed institutional reviews of drug utilization and served as consultants to all types of health-care facilities. In addition, when clinical pharmacists are active members of the care team, they enhance proficiency by: Providing critical input on medicine use and dosing. Working with patients to solve problems with their medications and improve compliance.

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“…Pharmacokinetic boosting of elvitegravir with ritonavir leads to systemic exposures that permit daily dosing. Alternatively, elvitegravir is co-formulated with cobicistat (see below) [35].…”

Section: Ritonavir and Cobicistatmentioning

confidence: 99%

Pharmacokinetic Enhancers (Boosters)—Escort for Drugs against Degrading Enzymes and Beyond

Krauß

Bracher

2018

Sci. Pharm.

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Pharmacokinetic enhancers (boosters) are compounds used in combination with a primary therapeutic agent (drug) and are not used for their direct effects on the disease but because they enhance or restore the activity of the primary agent. Hence, in certain cases, they represent an indispensable escort for enzyme-labile drugs. Pharmacokinetic enhancers can exert their activity on different ways. In the most common case, they inhibit enzymes such as human cytochrome P450 enzymes in the liver or other organs and, thereby, block or reduce undesired metabolism and inactivation of the primary drug. In this review, an overview will be given on the therapeutically most important classes of pharmacokinetic enhancers like β-lactamase inhibitors, inhibitors of CYP (cytochrome P450) enzymes in HIV therapy and hepatitis C, boosters for fluoropyrimidine-type anticancer agents, compounds utilized for enabling therapy of Parkinson’s disease with levodopa, and others. Inhibitors of efflux pumps in both pathogenic bacteria and tumor cells will be addresses shortly.

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Clinical Pharmacology in HIV Therapy

Cited by 81 publications

References 63 publications

Metabolic, mitochondrial, renal and hepatic safety of enfuvirtide and raltegravir antiretroviral administration: Randomized crossover clinical trial in healthy volunteers

Metabolic, mitochondrial, renal and hepatic safety of enfuvirtide and raltegravir antiretroviral administration: Randomized crossover clinical trial in healthy volunteers

Clinical Pharmacists in Chronic Care

Pharmacokinetic Enhancers (Boosters)—Escort for Drugs against Degrading Enzymes and Beyond

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