0000000000160334
AUTHOR
Virginia Melis
Estudio de interacciones farmacocinéticas del efavirenz con fármacos metabolizados por el CYP450: sertralina, nortriptilina y rifampicina.
En este trabajo se han estudiado las interacciones farmacocinéticas del efavirenz (EFV) con tres fármacos metabolizados por el citocromo P450 (sertralina (SRT), nortriptilina (NT) y rifampicina (RFP)), utilizando la rata como animal de experimentación. El EFV se administró por vía intraduodenal (dosis = 10 mg) y los otros fármacos se administraron por vía intraduodenal (SRT y NT) o por vía oral (RFP). La coadministración de EFV y SRT (dosis de 5 mg y 10 mg) dio lugar a niveles plasmáticos de EFV mayores que los obtenidos en el grupo de control (animales administrados solo con EFV). Cuando se administró la dosis de 10 mg de SRT, se obtuvo un incremento estadísticamente significativo en los v…
Determination of sertraline in rat plasma by HPLC and fluorescence detection and its application toin vivopharmacokinetic studies
A simple, rapid, and sensitive HPLC method based on 9H-fluoren-9-ylmethyl chloroformate derivatization for the quantification of sertraline in rat plasma has been developed, requiring a plasma sample of only 0.1 mL, which was deproteinized and derivatized for 5 min in two single steps. The obtained derivative was stable at room temperature and was determined by HPLC using a fluorescence detector. The analytical column was a C(18) column and the mobile phase was acetonitrile and water (80:20, v/v). Calibration curves were linear in the range of 10-500 ng/mL. The limit of detection was approximately 3 ng/mL, and the lower limit of quantification was established at 10 ng/mL. The bias of the me…
Nanoincorporation of curcumin in polymer-glycerosomes and evaluation of their in vitro–in vivo suitability as pulmonary delivery systems
The aim of this work was to deliver curcumin into the lungs by incorporating it into innovative vesicles obtained using phospholipids and high concentrations of glycerol (50%, v/v), so called glycerosomes, which were then combined with two polymers: sodium hyaluronate and trimethyl chitosan to form polymer-glycerosomes. These systems were prepared without the use of organic solvents or acidic solutions and their physico-chemical properties were fully characterized. Cryogenic transmission electron microscopy and small-angle X-ray scattering showed that both glycerosomes and polymer-glycerosomes were spherical, mainly unilamellar and of nanometric size (65–112 nm). The vesicles were readily n…
COMBINATION OF ARGAN OIL AND PHOSPHOLIPIDS FOR THE DEVELOPMENT OF AN EFFECTIVE LIPOSOME-LIKE FORMULATION ABLE TO IMPROVE SKIN HYDRATION AND ALLANTOIN DERMAL DELIVERY
Allantoin is traditionally employed in the treatment of skin ulcers and hypertrophic scars. In the present work, to improve its local deposition in the skin and deeper tissues, allantoin was incorporated in conventional liposomes and in new argan oil enriched liposomes. In both cases, obtained vesicles were unilamellar, as confirmed by cryo-TEM observation, but the addition of argan oil allowed a slight increase of the mean diameter (∼130nm versus ∼85nm). The formulations, especially those containing argan oil, favoured the allantoin accumulation in the skin, in particular in the dermis (∼8.7μg/cm(2)), and its permeation through the skin (∼33μg/cm(2)). The performances of vesicles as skin d…
Inhibition of Efavirenz Metabolism by Sertraline and Nortriptyline and Their Effect on Efavirenz Plasma Concentrations.
ABSTRACT Between 22 and 45% of HIV-positive subjects are likely to report symptoms of depression. Considering this background, a potential pharmacokinetic interaction between the nonnucleoside reverse transcriptase inhibitor efavirenz (EFV) and two antidepressants, sertraline (SRT) and nortriptyline (NT), was studied. Rats were administered EFV alone or together with the antidepressants, and changes in the plasma levels and pharmacokinetic parameters of EFV were analyzed. Additional in vitro experiments with rat and human hepatic microsomes were carried out to evaluate the inhibitory effect of SRT and NT on EFV metabolism by determining the formation rate of the major EFV metabolite (8-OH-E…
Inhalable polymer-glycerosomes as safe and effective carriers for rifampicin delivery to the lungs
Rifampicin loaded glycerosomes, vesicles composed of phospholipids, glycerol and water, were combined with trimethyl chitosan chloride (TMC) to prepare TMC-glycerosomes or, alternatively, with sodium hyaluronate (HY) to obtain HY-glycerosomes. These new hybrid nanovesicles were tested as carriers for pulmonary delivery of rifampicin. Glycerosomes without polymers were also prepared and characterized. All vesicles were similar: they were spherical, multilamellar and able to incorporate good amount of rifampicin (EE%∼55%). The addition of the polymers to the formulations allowed an increase of mean diameter. All the glycerosomes, in particular HY-glycerosomes, were able to deliver the drug to…
Pharmacokinetic Interaction between Nevirapine and Nortriptyline in Rats: Inhibition of Nevirapine Metabolism by Nortriptyline
ABSTRACTOne of the most frequent comorbidities of HIV infection is depression, with a lifetime prevalence of 22 to 45%. Therefore, it was decided to study a potential pharmacokinetic interaction between the nonnucleoside reverse transcriptase inhibitor nevirapine (NVP) and the tricyclic antidepressant nortriptyline (NT). NVP and NT were administered to rats either orally, intraduodenally, or intravenously, and the changes in plasma levels and pharmacokinetic parameters were analyzed. Experiments with rat and human hepatic microsomes were carried out to evaluate the inhibitory effects of NT on NVP metabolism. NVP plasma concentrations were significantly higher when this drug was coadminister…