Bioequivalency blood concentration curve

Phenytoin. Solid dispersions of phenytoin in PEG-4000,P l PEG-6000, and PVP were evaluated in vivo. The total areas under blood concentration curve (AUC) after oral administration to human volunteers were fourfold greater from a 1 10 PEG-4000 dispersion and 2.7-fold greater from a physical mixture than from phenytoin crystals. PEG-6000 dispersions (40% drug) were examined in mixed-breed dogs and compared with phenytoin sodium. Although phenytoin sodium dissolved several times faster in vitro than the solid dispersion of phenytoin, the two preparations were found to be bioequivalent. Sekikawa et al. " studied absorption of phenytoin in humans from PVP dispersions. The extent of bioavailability of phenytoin in phenytoin-PVP coprecipitate was 1.54 times greater than that of phenytoin alone. 

Fig. 1. Blood—drug concentration curve used to determine bioavailabiLitv and bioequivalence. C is the maximum dmg concentration in the blood and corresponds to some The AUC (shaded) represents the total amount of orally adininistered dmg the time from points A to B represents dmg onset, from points B to D, the duration MEC = minimum effective concentration MTC = minimum toxic concentration and TI = therapeutic index.

AC ADME ANS AUC BA/BE BBB BBM BBLM BCS BLM BSA CE CHO CMC CPC CPZ CTAB CV DA DOPC DPPC DPPH aminocoumarin absorption, distribution, metabolism, excretion anilinonaphthalenesulfonic acid area under the curve bioavailability-bioequivalence blood-brain barrier brush-border membrane brush-border lipid membrane biopharmaceutics classification system black lipid membrane bovine serum albumin capillary electrophoresis caroboxaldehyde critical micelle concentration centrifugal partition chromatography chlorpromazine cetyltrimethylammonium bromide cyclic votammetry dodecylcarboxylic acid dioleylphosphatidylcholine dipalmitoylphosphatidylcholine diphenylpicrylhydrazyl... 

Establishing clinical bioequivalence to a reference delivery method, usually a needle and syringe or an autoinjector or pen injector is the customary method of demonstrating that these conditions have been successfully met. This requires that the maximum blood plasma concentration of the drug (Cmax) and the total area under the time-concentration curve (AUC), as well as their associated confidence intervals, adequately approximate a reference product. The standard criteria to establish bioequivalence are 70-143% for Cmax and 80-125% for AUC (Fig. 3 for an example of a bioequivalent needle-free delivery). 

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