Influence of
Amiodarone on Urinary Excretion of
6b-Hydroxycortisol
in Humans
S.
MIČUDA1, M. HODAČ2, L. ŠIŠPERA1, P. PAŘÍZEK2, M. PLESKOT2,
G. ZIMOVÁ1, J. CERMAN3, J.
MARTÍNKOVÁ1, V. PIDRMAN2
1Department
of Pharmacology, 2Second
Department of Internal Medicine and 3Department
of Biochemistry, Faculty of Medicine, Charles
University, Hradec Králové, Czech Republic
Received June 28, 2000
Accepted August 16, 2000
Summary
The present study was undertaken to
evaluate the use of cortisol 6b-hydroxylation in
defining the effect of amiodarone on cytochrome
CYP3A activity. To accomplish this goal, the in
vivo activity of CYP3A was estimated by measuring
the 24-hour urinary excretion of
6b-hydroxycortisol (6b-OHC) and by calculating
24-hour ratio of 6b-hydroxycortisol to urinary
free cortisol (6b-OHC/UFC ratio). Nine cardiac
patients scheduled for amiodarone treatment were
recruited to participate in this study. Urine was
collected over a 24-hour period from each subject
before the first amiodarone administration and
during the third day of oral administration of
amiodarone (200 mg four times daily as a loading
dose). Three days of amiodarone treatment caused
a significant decrease (p<0.05) in both the
6b-OHC/UFC ratio and the 24-hour urinary
excretion of 6b-OHC. These results suggest that
amiodarone is an inhibitor of CYP3A activity.
Reprint
requests
Stanislav Mičuda, M.D., Department of
Pharmacology, Charles University in Prague,
Faculty of Medicine in Hradec Králové, Šimkova
870, 50001 Hradec Králové, Czech Republic.
fax.: +420-49-5513022, e-mail: micuda@lfhk.cuni.cz
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