Urinary 6-beta-OH-cortisol and paracetamol metabolites as a probe for assessing oxidation and conjugation of chemicals in humans.

The ratio between urinary 6-beta-OH-cortisol and 17-OH-corticosteroids was taken as an indirect estimate of monoxygenase activity in a population of controls and epileptic patients undergoing therapy with diphenylhydantoin and phenobarbital. Cortisol hydroxylation was increased in the group of epileptics with large inter-individual variations notwithstanding a similar dosage of inducers. The levels of some phase II conjugating enzymes were followed by administering paracetamol and measuring the urinary excretion of its main metabolites. Paracetamol glucuronate was increased by levels of cysteine and mercapturic derivatives of paracetamol did not vary, whereas sulfate derivatives were decreased in epileptic patients. Plasma N-acetyl-transferase activity did not vary in either group. Hydroxylated cortisol and paracetamol glucuronide excretion were not correlated in the same individuals, and no correlation was found between the ratio of 6-beta-OH-cortisol/17-OH-corticosteroids and the plasma levels of diphenylhydantoin or phenobarbital. Oxidation of cortisol and conjugation of paracetamol were controlled with different mechanisms, varied considerably between individuals and were not predictive of the pharmacokinetics of the inducers in treated patients.