In rats, CYP2C11 down-regulation was also demonstrated in chronic renal disease; however, no change in hepatic tolbutamide 4-hydroxylation was observed most probably due to the fact that tolbutamide is not selective for CYP2C11 contrary to the human CYP2C9 ortholog, but other CYPs are involved in the metabolism in rat [50]. Here, CYP2C9 is linked to chronic kidney disease.