Correlation Between In Silico Physicochemical Characteristics of Drugs and Their Mean Residence Time in Human and Dog

Int J Toxicol. 2012 Jan 20. Grabowski T, Jaroszewski JJ, Gad SC, Feder M.

The correlation between 52 physicochemical parameters and mean residence time (MRT) for 27 drugs used in human and dog were investigated. The physicochemical parameter values calculated provided a basis for deriving a series of arithmetic expressions, which were used to build a mathematical model describing the relationship between them and the MRT values. From the entire set of analyzed parameters, a subset of 14 was identified that contributed to the derivation of an arithmetic expression:Log(PSA - WPSA + ACID) × [XLogP - (LogKp - EA × Ln(Caco2 + AMINE + SAF)))] + + (AMIDE + IP - FG) - Ln(MW + PISA)the value of which is highly correlated with the MRT value in dogs (P < .001) and allowed prediction of the MRT predicted (MRT((pred))). In humans, no correlation was found that allowed the calculation of MRT((pred)). These results indicate that predicting the pharmacokinetics of any specific drug for humans based on pharmacokinetic data obtained in the dog should be undertaken with knowledge of the inherent limitations.