**9. Conclusion**

122 Toxicity and Drug Testing

Fig. 8. Franz diffusion cell used to measure skin permeability coefficients

p eff

log k 1.34 log k 0.28

coefficient, k*eff*, for a set of 31 compounds

permeability coefficients from aqueous solution, kp,

N 119, SD 0.461, R 0.832, F 112

2

permeability coefficient was a simple addition of terms in Eqn. 46

than hydrogen-bond donors.

p

The parallel artificial membrane permeability assay (PAMPA) has been suggested as a high throughput screening method for rapid determination of passive transport permeability in connection with gastrointestinal (GI) absorption (Sugano *et al*., 2002), blood-brain barrier penetration (Mensch *et al*., 2010 and skin permeation (Ottaviani *et al*., 2006). In the PAMPA method a 96-well filter plate coated with a liquid membrane is used to separate the donor and receptor compartments. Artificial membrane selection depends on the transport property to be determined. Ottaviani *et al*. (2006) found a reasonably accurate mathematical correlation between human skin permeability coefficient, kp, and the effective permeability

2

**EEABV**

(44)

k f p neutral p,neutral ionic p,ionic k f k (46)

(45)

N 31, SD 0.42, R 0.81, F 31

tested through an artificial membrane consisting of 70 % silicone and 30 % isopropyl myristate. The authors further noted that presence of isopropyl myristate as only a hydrogen-bond acceptor group in the artificial membrane was in accord with previous results demonstrating that stratum corneum lipids were better hydrogen-bond acceptors

Abraham and Martins (2004) reported an Abraham model correlation for human skin

Log k cm /s 5.426 – 0.106 – 0.473 – 0.473 – 3.000 2.296

based on a database containing 119 experimental values at a common temperature of 37 oC. The authors adjusted the experimental data for ionization by assuming that the measured

The Abraham solvation parameter model provides an in silico method for estimating ADMET properties of potential drug molecules in the early stages of drug discovery. To date mathematical expressions have been reported for predicting water-to-organic solvent partition coefficients and solubilities in more than 70 organic solvents, air-to-tissue and blood-to-tissue partition coefficients for 5 human and rat tissues, water-to-human skin and blood-to-rat/rabbit skin partitions, human skin permeability coefficients, and rat (Zhao *et al*., 2003) and human (Zhao *et al*., 2002) intestinal absorption. Expressions are also available for estimating Draize rabbit eye test scores for pure liquids and eye irritation thresholds in humans (Abraham *et al*., 2003), odor detection thresholds and nasal pungency of volatile organic compounds (VOCs) (Abraham *et al*., 2007b), and the minimum alveolar concentration (MAC) for inhalation anesthetics in rats (Abraham *et al.*, 2008b). The number of derived Abraham model correlations is expected in future years as more experimental data becomes available. Predictive applications require as input parameters the numerical values of the drug candidate's solute descriptors, which are easily calculable from measured solubility and partition coefficient data.
