Physicochemical Approaches to Drug Absorption

Plasma protein binding Polar surface area (A2) 

Reversed-phase high-performance liquid chromatography 

Calculated logarithm of the octanol/water partition coefficient (for neutral species) 

Daylight/Biobyte computer program for the calculation of log P Distribution coefficient (often in octanol/water) 

Difference between log P in octanol/water and alkane/water Transintestinal rate absorption constant (min-1) 

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Kerns, E. H., Di, L. Physicochemical profiling overview of the screens. Drug Discov. Today Technol. 2004, 1, 343-348. Van de Waterbeemd, H. Physicochemical approaches to drug absorption. In Drug Eioavailability (Methods and Principles in Medicinal Chemistry), Van de Waterbeemd, H., Lennernas, H., Artursson, P. (eds.), Wiley-VGH, Weinheim, 2003, pp. 3-20. 

Interesting approaches to affect intestinal absorption include drug physicochemical modification by either chemical derivatization or the use of delivery agents, low molecular weight peptide-like compounds that form a complex with the permeant. Generally, the transport of... 

More sophisticated approaches to predict the extent of oral absorption of drugs use mathematical models based on the known physiology and utilizing simple physicochemical measurements as input. The GastroPlus [4] program is a commercial tool that utilizes an advanced compartmental and transit model, based on the work of Amidon and Yu [5], and allows what-if questions to be posed to enable pharmaceutical optimization (see Chapter 17). For instance, the impact of morphology, formulation, and/or particle size changes, and sensitivity analysis to include errors in parameters on the prediction, can be considered. 

Mixed triglycerides formed by coupling of drugs to diglycerides exhibit physicochemical properties (120) and absorption characteristics (121)similar to those of natural triglycerides, resulting in a different pharmacokinetic and/or pharmacodynamic profile compared to that of the unmodified drug. Such an approach has been used to improve the oral systemic availability of phenytoin (122). 

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