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The influence of the structure of substituted benzodiazepines on their pharmacokinetic properties including the bioavailability, elimination half-life, clearance, and distribution volume in the human organism has been studied. The analysis was performed using the QSAR/QSPR method based on the Simplex representation of molecular structure. Completely adequate models capable of describing quantitatively the structure-pharmacokinetic properties relationship were obtained using the statistical methods of projection onto latent structures and multiple linear regression.Structural factors determining changes in the pharmacokinetic properties of substituted benzodiazepines are established on the basis of the obtained models.

We studied the effect of lauric acid on transdermal penetration of phenazepam in vivo. It was found that treatment with lauric acid 3-fold increased the maximum anticonvulsive effect of phenazepam applied in a transdermal therapeutic system in comparison with the control. Study of the pharmacokinetics of phenazepam transdermal therapeutic system showed its higher bioavailability in the presence of lauric acid (f=0.9).