6 beta-Hydroxycortisol: a noninvasive indicator of enzyme induction

Area of Science:

• Pharmacology
• Biochemistry
• Pediatrics

Background:

• The liver's microsomal mixed function oxidase system metabolizes drugs and foreign compounds.
• Assessing the induction of this system, particularly in children, is crucial for understanding drug metabolism and potential toxicity.
• Existing methods for assessing enzyme induction can be invasive or complex.

Purpose of the Study:

• To evaluate urinary 6 beta-hydroxycortisol (6 beta OHF) excretion as a noninvasive biomarker for microsomal mixed function oxidase system induction.
• To investigate the effect of anticonvulsant therapy on 6 beta OHF levels in children.

Main Methods:

• Measurement of urinary 6 beta-hydroxycortisol (6 beta OHF) excretion.
• Comparison of 6 beta OHF levels in normal children versus children on phenobarbital or diphenylhydantoin therapy.
• Analysis of metabolite ratios (5 beta OHF/17-hydroxycorticosteroid and 6 beta OHF/free cortisol).

Main Results:

• Urinary 6 beta OHF excretion increased 4- to 7-fold in children receiving anticonvulsant therapy.
• Elevated ratios of 5 beta OHF to 17-hydroxycorticosteroid and 6 beta OHF to free cortisol were observed.
• These findings suggest induction of the hepatic microsomal mixed function oxidase system.

Conclusions:

• Increased urinary 6 beta OHF excretion serves as a sensitive, noninvasive index of microsomal mixed function oxidase system induction in children.
• This method allows for rapid assessment of drug and xenobiotic compound effects on hepatic cortisol hydroxylation.
• The findings support the use of 6 beta OHF as a convenient probe for pediatric drug metabolism studies.