Lipophilic index

Each of these scales produce a lipophilicity index related but not identical to octanol-water partitioning. 

The lipophilicity index q>0 was defined by Valko et al. (1993). cpo is the volume percent of organic modifier in the mobile phase by which the retention time is twice the dead time, which means the retention factor k is equal to 1. It was reported that using the cpo scale, the inter laboratory comparability was improved compared to using log kw. The correlation with traditionally determined log Pow values was shown to better (Valko 1993) using the cpo index. The analytical advantage of the cpo value is that it can be estimated from bracketing experimental results and not from extrapolation to 0 % organic modifier. 

The CHI index was introduced by Valko et al. (1997) in order to match the lipophilicity index cpo... 

However, there are obvious differences between the classically determined octanol-water partition data and the reversed phase chromatographic partition data due to the different nature of the partitioning solvents. The correlation between shake flask octanol water partition coefficients and chromatographic retention factor kw (0 % organic solvent) was described to be low (Valko 2004) when structurally diverse compound sets were analysed. Using the q>o or the CHI lipophilicity index an improvement in agreement to logPow was reported (Valko 1993,1997). 

El Tayar, N. van de Waterbeemd, H. Testa, B. Measurements of protonated basic compounds by reversed-phase high-performance hquid chromatography II. Procedure for the determination of a lipophilic index by reversed-phase high-performance hquid chromatography. J. Chromatogr. 1985, 320, 305-312. 

The lipophilic index (log K 0) of methocarbamol was 1.54 as determined by correlation of HPLC retention times with those of formamide. Chromatographic conditions Nucleosil 5 C18 (4.6 mm i.d. x 150 mm), mobile phase - water (30-90%) methanol (70-10%), UV detection (220 nm), column temp 40°C27. 

Fig. 5.7 Correlation between relative pharmacological activity and lipophilic index of various acyl derivatives of insulin following intravenous injection in rats. The error bar represents the mean SE of three rats. 0.001, significantly different from native insulin by Student s...

The penetration-enhancing activities of monoterpenes, sesquiterpenes, and diter-penes were evaluated. Terpenes with relatively high lipophilic index exhibited absorption-promoting effects however, extremely high Upophilicity led to lower enhancing activities (Takayama et al., 1991). It was suggested that the difference in percutaneous absorption enhancing efficiency of terpenes arose from the difference in their thermodynamic activities in the vehicle (Obata et al., 1993). 

One of the simplest and most common ways to evaluate a molecule for ADME properties is a qualitative examination of its basic descriptor values such as molecular weight (MW), ClogP for lipophilicity, polar surface area (PSA), counts of hydrogen bond donors and acceptors (HBD, HBA), and count of rotatable bonds (RB). This type of approach popularized by Lipinski s famous Rule of 5 was published a decade ago [6]. Lipinski et al. established cutoffs for MW (500), ClogP (5), HBA (10), and HBD (5). These cutoffs were based on the 90th percentile of distributions of molecules in the World Drug Index having USAN or INN names. The Rule of 5 considers a violation of any two of these cutoffs to be an alert for poor absorption or permeability. 

The difficulty with HLB as an index of physicochemical properties is that it is not a unique value, as the data of Zaslavsky et al. (1) on the haemolytic activity of three alkyl mercaptan polyoxyethylene derivatives clearly show in Table 1. Nevertheless data on promotion of the absorption of drugs by series of nonionic surfactants, when plotted as a function of HLB do show patterns of behaviour which can assist in pin-pointing the necessary lipophilicity required for optimal biological activity. It is evident however, that structural specificity plays a part in interactions of nonionic surfactants with biomembranes as shown in Table 1. It is reasonable to assume that membranes with different lipophilicities will"require" surfactants of different HLB to achieve penetration and fluidization one of the difficulties in discerning this optimal value of HLB resides in the problems of analysis of data in the literature. For example, Hirai et al. (8 ) examined the effect of a large series of alkyl polyoxyethylene ethers (C4,C0, Cj2 and C 2 series) on the absorption of insulin through the nasal mucosa of rats. Some results are shown in Table II. 

The MA complex is lipophilic and dissolves in organic solvents and the distribution constant A),c is defined (index C for complex) ... 

Recently, Tichy investigated 41) the dependencies of the steric constants, Es, v, L, Bj, B4, MV (molar volume), [P] (parachor), MR (molar refraction), MW (molecular weight), and % (molecular connectivity index) on lipophilicity, as it is measured by n 42) and f43) constants. The data were treated by factor analysis methods. 

THC is optically active and the levorotatory form is 10 to 15 times more potent than the dextrorotatory. The therapeutic index (Tl) has been reported to be 40,000. Due to its lipophilicity, THC crosses the placental membrane and is stored in fat deposits in the body. In fact its pattern of appearance in the plasma is bimodal, that is, it shows up almost immediately after use to a certain extent and then reappears over a period of anywhere from 14 to 30 days as it is gradually released from fat stores and metabolized. The... 

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