Antoine Dupuis

Lopinavir to atazanavir or darunavir switch in HIV-1-infected patients with dyslipidemia: an observational study

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK

Plasma exchange significantly affects darunavir exposure

Sir, Plasma exchange (PE) is a therapeutic procedure aimed at reducing the amount of abnormal or toxic substances in the blood, e.g. immunoglobulins. It consists in removing a large volume of plasma from a patient and replacing it with some form of replacement fluid. PE is non-selective and may also remove circulating medications from blood (both protein-bound and unbound drug). Darunavir is a synthetic non-peptidic HIV protease inhibitor (PI) metabolized mainly by CYP3A4 isoenzymes and 95% bound by plasma proteins, primarily a-1-acid glycoprotein. Increased clearance of atazanavir, another PI, during PE has already been reported, but the effect of PE on darunavir disposition is unknown. Since darunavir exhibits concentration–effect relationships, knowledge of this effect is critical for treatment efficacy. We report here the case of a white woman in her 50s receiving highly active antiretroviral therapy (HAART) including darunavir and requiring PE treatment. Consent for publication was obtained from the patient. She was diagnosed HIV-1 positive in 2001 and started HAART in 2005. Viral load (VL) and CD4 count were 720956 copies/mL and 13 cells/mm, respectively, when she was hospitalized for visceral leishmaniasis with polyclonal hypergammaglobulinaemia. She then started a new HAART combination consisting of darunavir/ritonavir (600/100 mg twice daily) with emtricitabine/tenofovir (200/245 mg once daily). Despite good virological response (VL ,20 copies/mL), immunological restoration was not achieved (CD4 count1⁄4150 cells/mm and CD4/CD8 ratio1⁄40.08) and hypergammaglobulinaemia increased. Because of hyperviscosity syndrome, she underwent PE sessions twice a week during which darunavir pharmacokinetics (PK) were explored. Several blood samples were drawn over the dosing interval, i.e. just before, during and immediately after a 2 h PE session, in order to estimate the elimination rate constant during PE (keon); a plasma sample collected during PE was also assayed in order to determine the amount of darunavir eliminated by PE. Three additional samples were drawn after PE in order to estimate the darunavir elimination rate constant after a PE session (keoff). Plasma darunavir concentrations were determined using a validated HPLC-UV method and ke values were estimated as the slope from the linear regression of log-concentrations on sample times. Corresponding t1 2 were estimated as loge2 divided by ke. In order to demonstrate the impact of PE on steady-state darunavir PK profiles, PK simulations were performed using Nonmem population PK software (Monte Carlo simulation, n1⁄41000 concentration –time profiles). Calculated keon and mean estimated PK parameters obtained from the literature (CL/F1⁄410.7 L/h, V/F1⁄4198 L and ka1⁄40.95 h) were used for that purpose. PK analysis was performed during three PE sessions. The mean+SD plasma volume and darunavir amount removed per session were 2.51+0.03 L and 9.3+8.3 mg, respectively. Actual darunavir concentrations measured before, during and after PE sessions were 8802+4835, 4505+2930 and 3314+2103 ng/mL, respectively. Estimated keoff and keon were 0.10+0.1 and 0.53+0.13 h, respectively. These data

Les patients vivants avec le VIH (PVVIH) acceptent-ils les génériques dans la vraie vie ?

Introduction Dans l’optique de la reduction des couts, les recommandations du dernier rapport Morlat incitent a l’utilisation des generiques des traitements anti-retroviraux (ARV) actuellement disponibles pour le Truvada (TVD) et le Kivexa (KVX), notamment si le patient l’accepte, pouvant conduire au passage d’un traitement quotidien en un comprime par jour (STR) a un traitement en comprimes multiples (MTR). Nous avons voulu evaluer l’acceptabilite du passage aux generiques dans la vraie vie dans une cohorte de PVVIH. Materiels et methodes Entre le 01/11/2017xa0et 31/01/2018xa0tous les PVVIH traites efficacement (charge virale VIHxa0 Resultats Deux cent dix neuf patients ont ete inclus dans l’etude, repartis en 3xa0groupesxa0: groupe 1 (nxa0=xa095) sous TVD ou KVX plus un 3e agent, groupe 2 (nxa0=xa082) sous un STR pouvant etre remplace par un MTR, groupe 3 (nxa0=xa042) avec une combinaison d’ARV sans passage au generique possible. L’âge moyen de la cohorte etait de 51,9xa0ans [25–87], sex-ratio 1,8. Le passage au generique dans le groupe 1xa0a ete realise pour tous les patients permettant de diminuer le cout annuel des ARV de 284xa0665 € (2996€/an/patient). Parmi les patients du groupe 2 (47xa0hommes et 35xa0femmes) d’âge moyen 50,3xa0ans [28–77], 48xa0% (nxa0=xa039) ont accepte de prendre un MTR (soit une economie annuelle de 97xa0586 € ou 2502 €/an/patient)xa0; parmi les autres, le maintien du STR a ete motive par la peurxa0: de l’inobservance (nxa0=xa09), d’une intolerance (nxa0=xa02) et/ou d’un trop grand nombre de comprimes (nxa0=xa032). L’acceptation du passage d’un STR a un MTR etait liee au fait d’etre un homme (pxa0 Conclusion Les PVVIH ne s’opposent pas necessairement a la prescription de generiques, meme lorsqu’il s’agit de passer a un MTR, dans le but de reduire les couts de sante. Le passage vers les generiques a permis dans notre etude de reduire le cout annuel lie aux ARV de 382xa0251xa0euros. Dans la conjoncture actuelle, le patient doit etre implique a toutes les etapes de sa prise en charge et l’information concernant les generiques doit desormais s’inscrire pleinement a notre temps de consultation.

Preparation and Physico-Chemical Stability of Dexamethasone Oral Suspension

Abstract Background Dexamethasone is commonly used to treat a wide variety of diseases including oncological disorders. The aim of this study was to propose a liquid formulation of dexamethasone. Therefore we have developed and assessed the stability of a 5u2006mg/mL dexamethasone oral suspension. Methods A stability-indicating analytical method, using HPLC-UV, was developed and fully validated according to well-recognized international guidelines. The dexamethasone suspension was prepared using dexamethasone acetate powder and Ora-Sweet® plus Ora-Plus® suspending vehicles (1:1, v:v). Compounded oral suspension were packaged in amber type I glass bottles. In order to assess physical and chemical stability of dexamethasone in oral suspension, six batches of the formulation were prepared and stored at 4±2u2006°C or at 21±3u2006°C. Physical parameters (appearance, pH) were assessed as well as dexamethasone content, at day 0, 7, 14, 30 and 60. Results The mean dexamethasone concentration of the compounded oral suspensions was equal to 5.07±0.17u2006mg/mL. No colour modifications, precipitate or suspending troubles was observed throughout the storage period and the pH of the oral suspensions was decreased slightly, from 4.41±0.01 to 4.20±0.02. According to the dexamethasone content determined by HPLC-UV, whatever storage condition was used, no significant degradation of dexamethasone occurred over the 60 days of the study period. Conclusion Dexamethasone oral suspension prepared according to our conditions is stable over 60 days under regular storage temperatures (at 4±2u2006°C or at 21±3u2006°C).