Prediction of Clinically Relevant Safety Signals of Nephrotoxicity through Plasma Metabolite Profiling

Table 1

Sum of toxicity patterns matching phenytoin-induced metabolite changes.

Toxicity	Phenytoin, low dose	Phenytoin, high dose
Bone, osteoblast inhibitor	1
CNS, GABA receptor antagonist	2
Kidney, diuretic effect		1
Liver cholestasis		2
Liver toxicity		2
Liver, enzyme induction	1	5
Liver, paracetamol-derived toxicity		1
Thyroid, indirect effects	1	2
Grand total	5	13

Tabulation of the number of specific patterns associated with a given toxicity that: (1) have a confirmed match (see Section 2) with the metabolite profile of phenytoin treated animals at either the high or low dose, and (2) matched the metabolite profile of treated animals with a median correlation greater than 0.5 at either dose. Data taken from [25].