Partition coefficients apparent

Apparent partition coefficient (logZ)) at an ionic strength of / = 0.02M, log P value of the neutral microspecies and the acidic dissociation constant of 5 was calculated (97ANC4143). The distribution coefficient of 5 was determined between 1-octanol and universal buffer in the pH range 3-10 at a... 

In the traditional shake-flask method, the apparent partition coefficient, log D, is measured, usually at pH 7.4 (sometimes at pH 6.5). Different buffers are used to control each pH used in the determinations [70]. Usually, in a comprehensive study, several pH measurements are made, and values of log are plotted against the pH. This plot is often called the lipophilicity profile . One can determine the true partition coefficients (log P ) and the ionization constants from the features in such a curve. 

Sasaki, N. and Minato, M. (1983) Effect of the degree of supersaturation upon apparent partition coefficients of lead and strontium ions between BaSOa and aqueous solution. Miner. J., 11, 365-381. 

On the other hand, the ratio of total concentrations of ionized and nonionized species between both phases is named distribution coefficient (symbolized as D). It is often referred to as an effective or apparent partition coefficient and, in concentration terms, it is mathematically defined as ... 

Figure 2.1 Transport model diagram, depicting two aqueous cells separated by a membrane barrier. The drug molecules are introduced in the donor cell. The concentration gradient in the membrane drives the molecules in the direction of the acceptor compartment. The apparent partition coefficient, Kd = 2. [Avdeef, A., Curr. Topics Med. Chem., 1, 277-351 (2001). Reproduced with permission from Bentham Science Publishers, Ltd.]...

The limitation of Eq. (2.1) is that measurement of concentrations of solute within different parts of the membrane is very inconvenient. However, since we can estimate (or possibly measure) the distribution coefficients between bulk water and the membrane, log Kj (the pH-dependent apparent partition coefficient), we can convert Eq. (2.1) into a more accessible form... 

In all other sections of this book, we use the term Kp to represent the partition coefficient and Kd, the apparent partition coefficient. These terms were chosen to avoid symbol conflict when discussing permeability and diffusivity. Since this chapter and Chapter 5 are devoted primarily to partition coefficients, we will use the most common terminology P for partition coefficients and D for apparent (pH-dependent) partition coefficients. [Other symbols for these parameters have been used in the literature, including Pow (oil-water partition), Kqw, PC, and APC.]... 

The partition coefficient is needed to determine the moles lost to the membrane, VM CM(t). If ionizable compounds are considered, then one must decide on the types of partition coefficient to use -Kp (true pH-independent partition coefficient) or Kd (pH-dependent apparent partition coefficient). If the permeability assay is based on the measurement of the total concentrations, Cn(t) and CA(t), summed over all charge-state forms of the molecule, and only the uncharged molecules transport across the membrane to an appreciable extent, it is necessary to consider the apparent partition (distribution) coefficient, Kd, in order to explain the pH dependence of permeability. 

Note that from Eqs. (7.17) and (7.18), R EmCw(0/EpCp(O) for t > Tlag- The substitution of the apparent partition coefficient with the retention ratio allows us to state the mole balance at time t (provided t > Tlag) in a much simplified form ... 

Ketoprofen, a weak-acid drug, with a pKa 4.12 (25°C, 0.01 M ionic strength), was selected to illustrate Eqs. (7.20) and (7.21) in a series of simulation calculations, as shown in Fig. 7.16. The membrane-buffer apparent partition coefficients /(piii were calculated at various pH values, using the measured constants from... 

Each side of the barrier has a different membrane-buffer apparent partition coefficient Kd, defined at f = oo as... 

Figure 7.17 shows the asymmetry ratios of a series of compounds (acids, bases, and neutrals) determined at iso-pH 7.4, under the influence of sink conditions created not by pH, but by anionic surfactant added to the acceptor wells (discuss later in the chapter). The membrane barrier was constructed from 20% soy lecithin in dodecane. All molecules show an upward dependence on lipophilicity, as estimated by octanol-water apparent partition coefficients, log KdaA). The bases are extensively cationic at pH 7.4, as well as being lipophilic, and so display the highest responses to the sink condition. They are driven to interact with the surfactant by both hydrophobic and electrostatic forces. The anionic acids are largely indifferent... 

Four neutral lipid models were explored at pH 7.4 (1) 2% wt/vol DOPC in dode-cane, (2) olive oil, (3) octanol, and (4) dodecane. Table 7.5 lists the effective permeabilities Pe, standard deviations (SDs), and membrane retentions of the 32 probe molecules (Table 7.4). The units of Pe and SD are 10 6 cm/s. Retentions are expressed as mole percentages. Figure 7.22a is a plot of log Pe versus log Kd (octanol-water apparent partition coefficients, pH 7.4) for filters loaded with 2% wt/vol DOPC in dodecane (model 1.0, hlled-circle symbols) and with phospholipid-free dodecane (model 4.0, open-circle symbols). The dashed line in the plot was calculated assuming a UWL permeability (see Section 7.7.6) Pu, 16 x 10-6 cm/s (a typical value in an unstirred 96-well microtiter plate assay), and Pe of 0.8 x 10-6 cm/s... 

Figure 7.22 Lipophilic nature of membrane retention, log(%R) versus octanol-water apparent partition coefficient, pH 7.4, neutral lipid models.

Figure 7.23 Relative acceptor compartment concentrations versus octanol-water apparent partition coefficients [550]. [Reprinted from Kansy, M. Fischer, H. Kratzat, K. Senner, F. Wagner, B. Parrilla, I., in Testa, B. van de Waterbeemd, H. Folkers, G. Guy, R. (Eds.). Pharmacokinetic Optimization in Drug Research, Verlag Helvetica Chimica Acta Zurich and Wiley-VCH, Weinheim, 2001, pp. 447-464, with permission from Verlag Helvetica Chimica Acta AG.]...

Figure 7.24 Membrane retention in octanol-soaked filters versus octanol-water apparent partition coefficients.

Neutral molecules show a range of retention properties between those of acids and bases. Progesterone membrane retention is very high in all cases. Griseofulvin and carbamazepine retention steeply increase with phospholipid content. The patterns of retention follow the lipophilicity properties of the molecules, as indicated by octanol-water apparent partition coefficients (Table 7.4). 

The membrane permeabilities Pm may be converted to intrinsic permeabilities P(h when the pKa is taken into consideration. An ionizable molecule exhibits its intrinsic permeability when it is in its uncharged form and there is no water layer resistance. The relationship between Pm and P0 is like that between the pH-dependent apparent partition coefficient (log Kd) and the true partition coefficient (log Kp), respectively. This relationship can be rationalized by the mass balance. Take, for example, the case of a monoprotic acid, HA. The total substance concentration is... 

Figure 3.1 shows the appearance of dihydromethysticin in the acceptor well as a function of time [15], The solid curve is a least-squares fit of the data points to Eq. (1), with the parameters Pe = 32 x 10-6 cm s 1, R = 0.42, and t s = 35 min. The membrane retention, R, is often stated as a mole percentage (%R) of the sample (rather than a fraction). Its value can at times be very high - up to 90% for chlor-promazine and 70% for phenazopyridine, when 2% wt/vol DOPC in dodecane is used. Figure 3.2 shows a plot of log %R versus log Ka(7.4), the octanol/water apparent partition coefficient. It appears that retention is due to the lipophilicity of molecules this may be a good predictor of the pharmacokinetic volume of distribution or of protein binding. 

Zhou, X., Mopper, K. (1990) Apparent partition coefficients of 15 carbonyl compounds between air and seawater and between air and freshwater Implications for air-sea exchange. Environ. Sci. Technol. 24, 1864-1869. 

If, as might be expected, the unfilterable solid concentration covaries with the total solid concentration, then at high solid concentrations (KcMc> 1) a decrease in the apparent partition coefficient with increasing Me will result (see Morel and Gschwend, 1987). 

The physical as well as chemical interactions of a solute is capable of changing its apparent partition coefficient between a pair of solvents. Therefore, it is absolutely necessary to take this into consideration while selecting an appropriate extraction-system. Craig and Craig have advocated that the partition coefficients... 

Another approach to the same type of situation is simply to measure the distribution of total solute in both phases to provide a partition ratio that is sometimes referred to as an apparent partition coefficient. Obviously, for COM materials containing aliphatic acids or bases, this ratio can vary drastically with changes in pH. 

Ezumi, K. and Kubota, T. Simultaneous determination of acid dissociation constants and true partition coefficients by analyses of the apparent partition coefficient, Chem. Pharm. Bull, 28(1) 85-91, 1980. 

It is important to stress that, when measuring the simple concentration ratios of mean abundances in the solid and liquid phases formed at interface equilibrium (as is typically done in comparative studies), the resulting (apparent) partition coefficient is related to partition coefficient K valid at the interface, by... 

The ratio between equations 10.91 and 10.90 gives the relationship between apparent partition coefficient and conventional partition coefficient at interface K (i.e., the integrated form of eq. 10.84) ... 

Equation 10.93 clearly shows that, if apparent partition coefficient is adopted instead of conventional partition coefficient K actually valid at the solid/liquid interface to model Rayleigh s crystallization, errors arise whose magnitudes increase the more K differs from 1 and the longer the process advances. This is clearly shown in figure 10.15, in which fractional differences — K )IK are plotted as functions of T for various values of K . 

Table 10.7 Relationships between apparent partition coefficient and actual partition coefficient K for various ratios (from Albarede and Bottinga, 1972).

Oka Y. and Matsumoto T. (1974). Study on the compositional dependence of the apparent partitioning coefficient of iron and magnesium between coexisting garnet and clinopyro-xene solid solutions. Contrib. Mineral. Petrol, 48 115-121. 

The apparent partition coefficient (log P) and the calculated molar re-fractivity (CMR) are physicochemical parameters that correlate with the ability of a compound to be involved in MDR, and nonobvious structural homologies between compounds as dissimilar as verapamil (148) and vinblastine (1) exist as revealed by computer modeling studies (115). A far... 

In developing some of the relationships, it is helpful to use a four-quadrant diagram in which each quadrant represents a species in a lipid or water phase. The diagram below shows a typical distribution of an acid, AH, between two phases where ion partitioning is assumed to be negligible. The partition coefficent, P, is the ratio of the concentration of AH in the octanol to the concentration of AH in the aqueous phase. The distribution coefficient, D, is the ratio of the concentration in the octanol to that of all forms in the water. This is also called the apparent partition coefficient. 

Apoplastic transport, achieving, 197 Apparent partition coefficient, 227 Area, relationships, 260 Artificial diet feeding assay, 163-64 2-Ary1-1-cycloalkanediones biological properties, optimization, 321 structure-activity... 

Papp is the apparent partition coefficient that varies with pH. Thus it can be seen when a compound, acid or base, is 50% ionised (i.e. pH = pA a) its partition coefficient is half that of the drug in the un-ionised state ... 

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