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Eur J Clin Pharmacol. 2003 Dec;59(10):713-33. Epub 2003 Nov 6.

Urinary 6beta-hydroxycortisol: a validated test for evaluating drug induction or drug inhibition mediated through CYP3A in humans and in animals.

Author information

1
Laboratoire du Centre de Médecine Préventive, 2 rue du Doyen Parisot, 54500, Vandoeuvre-Les-Nancy, France. MM.Galteau@cmp.u-nancy.fr

Abstract

6beta-Hydroxycortisol (6beta-OHF) urinary excretion has, for a long time, been considered a marker of drug induction and, more recently, of drug inhibition in humans and in laboratory animals, but its specificity is still under debate. In this work, we review 277 papers devoted to 6beta-OHF urinary excretion. We have evaluated factors that could modify 6beta-OHF excretion and, thus, could explain contradictory results. We have examined the effect of the analytical techniques on physiological values. Intra- and inter-individual variability and the effect of circadian rhythms on urinary excretion of 6beta-OHF as well as cortisol and 17-hydroxycorticosteroids have been evaluated. We also give an overview of drugs that induce, inhibit or have no effect on 6beta-OHF. For inducing and inhibiting drugs, we calculated the ranges of variation of 6beta-OHF excretion from the results indicated in the different papers. This work was done for well-known inducers, such as anticonvulsants, but also for other inducing or inhibiting drugs found in the literature. The time-course of variation in 6beta-OHF excretion when different drugs are co-administered was also investigated. The potential relationship between cytochrome P(450) 3A4 (CYP3A4) polymorphism and 6beta-OHF excretion was studied. Finally, the interest of 6beta-OHF urinary excretion was compared with that of other tests proposed to measure CYP3A4 activity. This review demonstrates that 6beta-OHF urinary excretion is a good test to evaluate drug-metabolising enzyme inducing or inhibiting properties of drugs when the subjects are their own controls, but this test is not reliable enough to measure actual CYP3A4 activity.

PMID:
14605790
DOI:
10.1007/s00228-003-0690-3
[Indexed for MEDLINE]

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