Preclinical safety assessment of contrast media: predictive value

Abstract

The purpose of preclinical tests is to identify the potential benefits and risks of new diagnostic or therapeutic products. Regarding iodinated contrast media (CM), LD50 tests were used extensively in the past. However, from both scientific and ethical perspectives, it is today highly relevant to question the use of LD50 tests. Due to species differences and the very high volume of CM needed to kill half of the animals, such tests are not sensitive enough to differentiate between modern nonionic CM. Further, they are not very predictive in terms of human tolerability. In other tests with more relevant end-points than death, overall tolerance to the new dimeric compound iodixanol (Visipaque), representing the latest step in the development of CM, has been shown to be higher than to the nonionic monomers. Clinical experience has shown that the physiological parameters often stay closer to baseline after Visipaque than after administration of conventional CM.

Iodinated radiographic contrast media possess antioxidant properties in vitro

“…Iodinated radiographic contrast media (IRCM) for intravascular use (Table 1) are tri-iodinated derivatives of benzoic acid (1). In addition to absorbing Xrays, they all have biological properties that may affect a variety of physiological processes (23). Few if any pharmaceutical agents are used at such a high plasma concentration as IRCM (2).…”

Quantitative Retention (Structure)–Activity Relationships in Predicting the Pharmaceutical and Toxic Properties of Potential Pesticides

“…The physicochemical, pharmacokinetic, and toxicity parameters of the compounds ( Table 2 ) are as follows: the logarithm of the partition coefficient (log P ) in the n -octanol/water system, the number of hydrogen bond donors ( HBD ), acceptors ( HBA ), and rotatable bonds ( NRB ), molar weight ( MW ), topological polar surface area ( TPSA ) [ 24 ], the volume of distribution in the body ( V d ) [ 25 ], the fraction unbonded in a brain ( f u, brain ), in plasma ( f u, plasma ) [ 26 ], and pharmacokinetic parameters describing blood–brain distribution (log BB ) [ 26 , 27 , 28 , 29 ], the rate of permeation from aqueous solutions through skin (log K p ) [ 30 , 31 ], skin–water partition coefficient (log K sc ) describing dermal absorption from aqueous solutions [ 32 , 33 ], the rate of permeation through cell (log K w/cell ) [ 34 ], partitioning between water and serum albumin (log P w/HSA ), and binding to human serum albumin (log K HSA ) [ 10 , 35 , 36 , 37 ], partitioning between water and plant’ cuticles (log P w/pc ) [ 38 ], and the dose causing the death of 50% of the group of mice tested after oral administration ( LD 50 ) [ 39 , 40 ]. These parameters describe important properties of the test substances and provide information about their potential applications as pesticides as well as potential threats to humans [ 41 , 42 ].…”