Interacciones medicamentosas en pacientes infectados con el VIH: aproximación para establecer y evaluar su relevancia clínica

Abstract

Among patients with HIV/AIDS, most of the pharmacokinetic interactions of clinical relevance are attributed to inhibition or induction of hepatic systemic metabolic activity, mainly of CYP3A4.

Relevancia clínica de las interacciones medicamentosas en pacientes infectados con el virus de la inmunodeficiencia humana: actualización 2015-2017

“…Por ello, las IM son un tema relevante relacionado con la farmacoterapia de pacientes con infección por VIH/SIDA. En este sentido, se han realizado varias revisiones sobre el tema [5][6][7][8] ; sin embargo, dicha información requiere ser actualizada, debido a la comercialización de nuevos anti-retrovirales (ARVs) y, especialmente, a la identificación de nuevas IM o a la generación de nueva información de IM previamente identificadas.…”

Clinical Relevance of Drug Interactions in HIV-Infected Patients Receiving Antiretroviral Therapy

“…Thus, it is important to present a development proposal, which have been adjusted with goal to evaluate and predict the clinical relevance of pharmacokinetic DIs in HIV-infected patients receiving ARV therapy. (Amariles et al, 2007b;Giraldo et al, 2010) 2.2.1 Identifying and assessing if one of the medication that the patient is using (or that the patient will be use) is considered as a drug with narrow therapeutic indices The therapeutic index of a drug is the ratio of the dose that produces toxicity (drug plasma concentration that elicits the toxic effect in 50 percent of treated individuals -TD 50 -), and the dose that produces a clinically desired or effective response in a population of individuals (drug plasma concentration that elicits the therapeutic effect in 50 percent of the treated individuals -ED 50 -) as shown in equation 1 (Katzung, 2009) Both TD 50 and ED 50 are calculated from dose response curves, which represent the frequency with which each drug plasma concentration elicits the therapeutic effect or the toxic effect in the population (figure 2). From a clinical perspective, drug therapeutic range corresponds at drug plasma concentrations associate to likelihood of achieving, in the most patients, the maximum therapeutic effect with the minimum toxic effect.…”

“…Thus, almost 80% of pharmacokinetic DIs are related to changes in systemic clearance, mainly associated to the systemic inhibition or induction of the metabolic activity of the CYP450 isoenzymes, and approximately 15% related to changes in bioavailability (changes in gastrointestinal pH, presystemic clearance [by hepatic or intestinal CYP3A4 isoenzyme]) or by in P-gp activity). (Amariles et al, 2007b;Giraldo et al, 2010) Because a near to 80% of clinically relevant pharmacokinetic DIs are related to hepatic metabolism, both systemic and presystemic, during the process of developing new drugs it is important to characterize and to predict DIs related to hepatic metabolism. With this goal, both cell cultures are used to establishing the ability of the new drug to modify the activity of major CYP450 isoenzymes, and the assessment of the susceptibility of the drug metabolism to be affected by drugs recognized as enzyme inhibitors and inducers.…”

“…In this way, a proposal to identify, evaluate, and predict DIs considered as clinically relevant is presented, in which clinical relevance of a DI is defined according to the probability of their occurrence and to the severity of clinical effect in patient health (adverse event or therapeutic failure). (Amariles et al, 2007a) Previous review about DIs with ARV, (Amariles et al, 2007b;Giraldo et al, 2010) achieved as a result of searched in Pubmed/Medline database, have showed that, in the case of clinically relevant pharmacokinetic interactions, nearly 80% are related to changes in systemic clearance, mainly associated to the systemic inhibition or induction of the metabolic activity of the cytochrome P-450 (CYP-450), mostly CYP3A4 isoform, whereas approximately 15% are related to changes in bioavailability (changes in gastrointestinal pH, presystemic clearance [mediated by CYP3A4 hepatic or intestinal]) or in P-glycoprotein activity). (Amariles et al, 2007b;Giraldo et al, 2010) For this chapter, the earlier published information (Amariles et al, 2007a(Amariles et al, , 2007bGiraldo et al, 2010;Amariles, 2002.…”

“…(Amariles et al, 2007a) Previous review about DIs with ARV, (Amariles et al, 2007b;Giraldo et al, 2010) achieved as a result of searched in Pubmed/Medline database, have showed that, in the case of clinically relevant pharmacokinetic interactions, nearly 80% are related to changes in systemic clearance, mainly associated to the systemic inhibition or induction of the metabolic activity of the cytochrome P-450 (CYP-450), mostly CYP3A4 isoform, whereas approximately 15% are related to changes in bioavailability (changes in gastrointestinal pH, presystemic clearance [mediated by CYP3A4 hepatic or intestinal]) or in P-glycoprotein activity). (Amariles et al, 2007b;Giraldo et al, 2010) For this chapter, the earlier published information (Amariles et al, 2007a(Amariles et al, , 2007bGiraldo et al, 2010;Amariles, 2002. ) have been complement with information achieved from both a structured and systematic review of publications on Pubmed/Medline and references cited in relevant articles, and in other electronic databases (SIETES, MEDSCAPE, and TRIPDATABASE), and supplemented by other primary and secondary information sources to identify DIs in HIV-infected patients.…”