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[2] Absorption is the bottleneck, not concentration alone

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In both rats and humans administered APAP, the endogenous quantities of p -cresol sulfate in the urine were correlated with liver effects (rat)37 and the APAP-sulfate/APAP-glucuronide ratio (humans),38 directly leading to the concept of pharmacometabonomics.37,38 Similarly, urinary concentrations of p -cresol and p -cresol sulfate have been found to be elevated in children with autism39 and when the urinary APAP-sulfate/APAP-glucuronide ratio was determined for 20 low functioning autistic children receiving the drug it was found to be significantly lower than for the controls.40 The prediction of acute APAP-induced liver injury in humans, and consequent treatment needs or patient outcomes during hepatotoxicity remains difficult