Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2486343 | Journal of Pharmaceutical Sciences | 2011 | 8 Pages |
Abstract
In the present work, a single modelâindependent approach was developed to optimize the release kinetics of drugs from sustainedârelease formulations, using stavudine (d4T) as a model drug. This approach is based on the pharmacokinetic simulation of drug plasma levels through a semiparametric approach of the input function and on convolution with an empirical polyexponential unit impulse response function. Input functions were evaluated using different zeroâorder and firstâorder release constants. Optimum drug release to obtain a specific pharmacokinetic profile was approached using target modelâindependent pharmacokinetic parameters such as CmaxSS, CminSS, tmaxSS, and peakâtrough fluctuations. A Monte Carlo simulation was performed to estimate the fractional attainment of d4T plasma concentrations over therapeutic d4T levels. Zeroâorder (K0 = 4 mg/h) and firstâorder (K1 = 0.05 hâ1) release constants were optimal for the formulation of sustainedârelease d4T tablets, plasma concentrations within the therapeutic range being achieved. © 2011 WileyâLiss, Inc. and the American Pharmacists Association J Pharm Sci 100:3260-3267, 2011
Keywords
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Pharmacology, Toxicology and Pharmaceutical Science
Drug Discovery
Authors
Cristina Maderuelo, Aránzazu Zarzuelo, José M. Lanao,