fulltext.study @t Gmail

Oral pharmacokinetics of the anti-HIV efavirenz encapsulated within polymeric micelles

Paper ID Volume ID Publish Year Pages File Format Full-Text
7426 552 2011 9 PDF Available
Title
Oral pharmacokinetics of the anti-HIV efavirenz encapsulated within polymeric micelles
Abstract

Aiming to improve the pediatric pharmacotherapy of the human immunodeficiency virus (HIV) infection, our group has recently developed a concentrated formulation of the first-line antiretroviral efavirenz by means of encapsulation within polymeric micelles. The aqueous solubility of the drug was increased more than 8400 times (up to 34 mg/mL) and preliminary preclinical data suggested the significantly greater oral bioavailability with respect to an extemporaneous suspension and an oleous solution (similar to the only “commercially available” pediatric formulation). As the preamble to a bioequivalence trial to evaluate the micellar system in adult healthy volunteers, the present work investigated the effect of parameters such as dose per body weight and drug concentration on the oral pharmacokinetics of the drug. The non-linear pharmacokinetics of the drug was confirmed for all the formulations. Despite the drug concentration and dose, micelles consistently resulted in significantly greater absorption rates, PK parameters increasing up to 3-fold. For example, Cmax values increased from 687, 1789 and 2657 ng/mL for the oily system to 1145, 2856 and 7056 ng/mL for the micellar one, for EFV doses between 20 and 80 mg/kg. Data clearly showed that the smaller the micellar size, the higher the bioavailability attained. The effect of micellar size was also assessed. In addition, a comparison between in vitro dissolution rates of EFV for the different micelles and AUC values suggested that micelles releasing faster in vitro lead to a less pronounced absorption in vivo. These findings would suggest the involvement of additional absorption mechanisms.

Keywords
Pediatric HIV/AIDS pharmacotherapy; Pure and mixed micelles; Efavirenz-loaded poloxamer and poloxamine micelles; Improved oral pharmacokinetics
First Page Preview
Oral pharmacokinetics of the anti-HIV efavirenz encapsulated within polymeric micelles
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 32, Issue 9, March 2011, Pages 2379–2387
Authors
, , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us