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First published on October 6, 2009
The Journal of Clinical Pharmacology 2009, doi:10.1177/0091270009344336
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©© 2009 American College of Clinical Pharmacology, Inc.
The Journal of Clinical Pharmacology, 10.1177/0091270009344336

Article

Effect of Thyroid Hormone on the Activity of CYP3A Enzyme in Humans

Norio Takahashi 1, Naoki Inui 1*, Hiroshi Morita 1, Kazuhiko Takeuchi 1, Shinya Uchida 2, Hiroshi Watanabe 1, and Hirotoshi Nakamura 1

1 Hamamatsu University School of Medicine
2 University of Shizuoka

* To whom correspondence should be addressed. E-mail: inui{at}hama-med.ac.jp.


  Abstract
Thyroid hormones have been shown to reduce the activity and expression of cytochrome P450 (CYP) 3A4 in vitro. The influence of thyroid hormone on drug action via a CYP3A-dependent pathway has not been elucidated in humans. This is the first report showing the effect of thy roid hormone on CYP3A enzyme activity in humans. Ten healthy volunteers participate in this open-label study, in which the pharmacokinetics of midazolam and the urinary ratios of 6 {beta}-hydroxycortisol/free cortisol before and after 2 weeks of oral administration of triiodothyronine were compared. Triiodothyronine administration significantly reduced the area under the concentration–time curve ratios for 1'-hydroxymidazolam/midazolam from 0.36 to 0.25 (P < .05) and urinary ratios of 6 {beta}-hydroxycortisol/ free cortisol from 6.92 to 5.88 (P < .05). These results strongly suggested that thyroid hormone reduced CYP3A activity in human and may influence the pharmacokinetics of concomitant CYP3A substrate drugs.
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