Pharmacokinetics of Susalimod, a Highly Biliary‐excreted Sulphasalazine Analogue, in Various Species. Nonpredictable Human Clearance by Allometric Scaling

The pharmacokinetics of susalimod (2-hydroxy-5-((4-((3-methyl-2-pyridinylamino)sulphonyl)phenyl)-ethynyl)-benzoic acid) were investigated in various animal species and in man after intravenous administration. Plasma clearance was expected to correlate mainly to biliary clearance, since susalimod is excreted approximately 90% unchanged in bile. Biliary excretion was also the main route in man, based on a high recovery in faeces. Susalimod was rapidly eliminated from plasma in all animal species (t½ < 0.5 h) but was much slower in man (t½ = 16 h). Allometric scaling of the preclinical clearance showed a very good correlation (r = 0.947) between the different animal species. However, the predicted human clearance was 20-times higher than the observed clearance. Susalimod is an example of a biliary-excreted compound exhibiting a much slower elimination rate in man compared with animals, resulting in nonpredictable human clearance by allometric scaling of preclinical data.