Partition coefficient, of a drug

The partition coefficient of a drug is defined as the equilibrium constant... 

The lipid-aqueous partition coefficient of a drug molecule affects its absorption by passive diffusion. In general, octanol/pH 7.4 buffer partition coefficients in the 1-2 pH range are sufficient for absorption across lipoidal membranes. However, the absence of a strict relationship between the partition coefficient of a molecule and its ability to be absorbed is due to the complex nature of the absorption process. Absorption across membranes can be affected by several diverse factors that may include the ionic and/or polar characteristics of the drug and/or membrane as well as the site and capacity of carrier-mediated absorption or efflux systems. 

These v values are characteristic for the substituent and can be used to calculate how the partition coefficient of a drug would be affected by adding these substituents. The P value for the lead compound would have to be measured experimentally, but once that is known, the P value for analogues can be calculated quite simply. 

Equation 9.25 is used conventionally to calculate the partition coefficient of a drug. In Equation 9.25, Cq, the concentration of drug in the organic or oil phase, is divided by the concentration in the... 

In a similar manner, the partition coefficient of a drug between the skin and the vehicle can be expressed as ... 

It is poorly soluble in acetone, 2-butanone, ethyl acetate, acetonitrile, and DMF, and insoluble in alcohols, petroleum ether, and diethyl ether. The partition coefficients of a number of solutes between PCL and water have been measured and correlated with octanol-water partition coefficients (Fig. 9) (58,59). The linear correlation (Eq. 2) when combined with the water solubility of the solutes serves as a method of estimating the solubility of drugs in PCL from first principles. ... 

Avdeef, A., Box, K. J., Comer, J. E., Hibbert, C., Tam, K. Y. pH-metric logP 10. Determination of liposomal membrane-water partition coefficients of ionizable drugs. Pharm. Res. 1998,... 

Bouchard, G., Galland, A., Garrupt, P. A., Gulaboski, R., Mirceski, V., Scholz, F., Girault, H. H. Standard partition coefficients of anionic drugs in the n-octanol/water system determined by voltammetry at three-phase electrodes. Phys. Chem. Chem. Phys. 2003, 5, 3748-3751. 

Use of the relatively small cyclopropane ring drastically reduces the potential for deleterious steric bulk effects and adds only a relatively small lipophilic increment to the partition coefficient of the drug. One of the clever elements of the rolicyprine synthesis itself is the reaction of d,l tranylcypromine (67) with L-5-pyrrolidone-2-carboxylic acid (derived from glutamic acid) to form a highly crystalline diastereomeric salt, thereby effecting resolution. Addition of dicyclohexylcarbodiimide activates the carboxyl group to nucleophilic attack by the primary amine thus forming the amide rolicyprine (68). 

I. Lipid-soluble drugs cross the membrane at a rate proportional to the concentration gradient across the membrane and the lipid water partition coefficient of the drug... 

Bard, B., Carrupt, P.A. and Martel, S. (2009) Determination of partition coefficients of basic drugs using hydrophilic interaction chromatography. Journal of Medicinal Chemistry, 52, 3416-3419. 

The permeability, P (P = Pc x D), of a nonpolar substance through a cell membrane is dependent on two physicochemical factors (1) solubility in the membrane (Pc), which can be expressed as a partition coefficient of the drug between the aqueous phase and membrane phase, and (2) diffusivity or diffusion coefficient (D), which is a measure of mobility of the drug molecules within the lipid. The latter may vary only slightly among toxicants, but the former is more important. Lipid solubility is therefore one of the most important determinants of the pharmacokinetic characteristics of a chemical, and it is important to determine whether a toxicants is readily ionized or not influenced by pH of the environment. If the toxicant is readily ionized, then one needs to understand its chemicals behavior in various environmental matrices in order to adequately assess its transport mechanism across membranes. 

From Figure 2, it is apparent that there is also a partitioning step as the drug diffuses from the stratum corneum to the viable tissue, this can be described by a backward rate constant, kj. Empirically it has been shown that the ratio kg/k2 can be related to the octanol-water (pH 7.4) partition coefficient of the drug divided by... 

A permeation experiment was carried out with a freshly made membrane. It was determined that the diffusion coefficient of a drug is 3.1 x 10-3 cm2/hr, the partition coefficient is 0.15, the thickness of the membrane is 0.1 cm, the solubility of the drug is 2 mg/mL, the volume of the reservoir is 0.314 cm2, and the total drug amount present in the reservoir is 1 mg. Calculate the cumulative amount of drug release for 30 hr. 

The rate of diffusion of a topically applied toxicant across the rate-limiting stratum corneum is directly proportional to the concentration gradient across the membrane, the lipid/water partition coefficient of the drug, and the diffusion coefficient for the compound being studied. This can be summarized by Fick s law of diffusion in the equation... 

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