Modifications in other sites further reduced the overall lipophilicity (logP), which in turn decreased the interaction of the drug with lung surfactants and reduced its accumulation in the kidneys. These changes significantly improved the in vivo safety profile . Notably, the significant effects on toxicity caused by subtle stereochemical modifications and positioning of the halogen substituent on the benzyl ring of the new lipid tail [117] highlighted how toxicity is not only influenced by physicochemical properties but likely involves other complex mechanisms (e.g., interactions with peptide transporters in the kidneys are likely important ).