Link between drug absorption solubility and permeability measurements in Caco-2 cells.
The objective of this investigation was to establish a relationship between drug permeability and solubility in vitro and the extent of drug absorption in humans. We selected drugs with varying permeabilities and solubilities with the aim of establishing a relationship between permeability and solubility measurements in vitro and the extent of absorption in vivo. Effective permeability coefficients of the model drugs (naproxen, phenytoin, propranolol, diltiazem, salicylic acid, ephedrine, cimetidine, chlorothiazide, and furosemide) at 37 degrees C and pH 7.2 were estimated using the Caco-2 cell line. Saturation solubilities of the model drugs were estimated at pH 7.2 and at 37 degrees C. Data obtained from the permeability and solubility experiments were employed in classifying the drugs into high and low permeability-solubility groups. The permeability coefficients ranged from 1x10(-7) to 4x10(-5) cm/s, and a good correlation was observed between the permeability coefficients in Caco-2 cells and percent absorbed in humans. Drugs in the high permeability, high solubility class are completely absorbed (90% or higher). The study results indicate that there is a strong link between permeability measured in Caco-2 cells, solubility, and fraction of drug absorbed in humans.
Pade
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Pharmaceutics Division, College of Pharmacy, The University of Texas at Austin, 78712, USA.
Stavchansky
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S
D000042:Absorption / Q000502:physiology; D018938:Caco-2 Cells / Q000502:physiology*; D002463:Cell Membrane Permeability / Q000502:physiology; D006801:Humans; D010599:Pharmacokinetics; D012995:Solubility