Vangelis Karalis

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Oseltamivir was administered at 1.0 mg/kg b.i.d. to 13 neonates exposed to influenza H1N1. No influenza, neurologic, or laboratory adverse effects occurred. The mean Cmax values for oseltamivir and oseltamivir carboxylate were found to be lower than those reported for children 1 to 5 years old, whereas Tmax values were similar to children 1 to 5 years old.(More)
Unveil the properties of a two-stage design (TSD) for bioequivalence (BE) studies. A TSD with an upper sample size limit (UL) is described and analyzed under different conditions using Monte Carlo simulations. TSD was split into three branches: A, B1, and B2. The first stage included branches A and B1, while stage two referred to branch B2. Sample size(More)
Generics are usually considered to exhibit comparable in vivo properties in terms of efficacy and safety and for this reason are intended to be interchangeable with the reference product. The aim of this study is to provide a quantitative picture of the switchability problem between two generics and to introduce the concept of conditional probability of(More)
To explore the comparative performance of the recently proposed bioequivalence (BE) approaches, FDAs and EMAs, by the FDA working group on highly variable drugs and the EMA, respectively; to compare the impact of the GMR-constraint on the two approaches; and to provide representative plots of % BE acceptance as a function of geometric mean ratio, sample(More)
Two-stage designs (TSDs) are currently recommended by the regulatory authorities for bioequivalence (BE) assessment. The TSDs presented until now rely on an assumed geometric mean ratio (GMR) value of the BE metric in stage I in order to avoid inflation of type I error. In contrast, this work proposes a more realistic TSD design where sample re-estimation(More)
(1) To develop novel scaled bioequivalence (BE) limits with levelling-off properties based solely on variability considerations and (2) to evaluate their performance in comparison to the classic unscaled BE limits 0.80–1.25, the expanded BE limits 0.75–1.33 and the recently proposed Geometric Mean Ratio (GMR)-dependent scaled BE limits BELscW (Karalis et(More)
The purpose of the present work is to develop a non-binary biopharmaceutical classification system the so called ABΓ system. The original mathematical model used for the development of BCS, appropriately modified, was applied to estimate the limiting values of drug solubility and permeability when the fraction of dose absorbed, Fa, was 0.90 or 0.20. The ABΓ(More)
In this study, novel approaches for the design of bioequivalence (BE) limits are developed. The new BE limits scale with intrasubject variability but only until a geometric mean ratio (GMR)-dependent plateau value and combine the classic (0.80-1.25) and expanded (0.70-1.43) BE limits into a single criterion. Plots of the extreme GMR values accepted as a(More)
Purpose. To explore the quantitative structure pharmacokinetic relationships of the disposition parameters: clearance (CL), apparent volume of drug distribution (V ap), fractal clearance (CL f), and fractal volume (v f) for 272 structurally unrelated drugs used in therapeutics. Methods. Literature data were used for CL and V ap whereas CL f and v f were(More)
The combination of fluticasone propionate (FLP) and salmeterol (SAL) is often used in clinical practice for the treatment of pulmonary disorders. The purpose of this study was to explore the pharmacokinetics (PK) of inhaled FLP and SAL, after concomitant administration, in healthy male and female subjects using two dry powder inhalers. Plasma concentration(More)