Correlations between no observed effect level and selected parameters of the chemical structure for veterinary drugs.
No observed effect level (NOEL) represents the lowest value among numerous parameters used for the analysis of risk and the safety of a chemical substance and medicinal product. In the present study, the correlation between NOEL and selected topological parameters was determined for a group of 135 veterinary drugs. Due to the high values of the standard deviation for most of the parameters, the method of NOEL mean values analysis in quintile groups was used. The direct correlations between NOEL and the partition coefficient octanol/water (LogKOW), logarithm of water solubility value (LogSw), polar surface area (PSA), apolar surface area (aPSA), hydrogen bond acceptors and hydrogen bond donors were very low. In quintile groups a significant correlation (P<0.05) between NOEL and LogKOW, aPSA, PSA, as well as between NOEL and equations based on topological parameters were found. The results obtained indicate that, among the analysed parameters, LogSw and PSA play a crucial role in relation to a drug activity, at the NOEL level, in the tested group of compounds. Moreover, the calculation tools, based on the analysis of the molecular structure of topological parameters, can be useful for the prognosis of parameters describing drug safety.
Grabowski
Tomasz
T
Centre of Pharmacokinetics Research FILAB, 05-119 Łajski, Poland. t.grabowski@filab.com.pl
Jaroszewski
Jerzy Jan
JJ
Piotrowski
Walerian
W
D003198:Computer Simulation; D006860:Hydrogen Bonding; D019055:No-Observed-Adverse-Effect Level; D012984:Software; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013329:Structure-Activity Relationship; D013499:Surface Properties; D019155:Veterinary Drugs / Q000737:chemistry* / Q000494:pharmacology*
D012997:Solvents; D019155:Veterinary Drugs