Effect of thyroid hormone on the activity of CYP3A enzyme in humans.
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 thyroid 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.
Takahashi
Norio
N
Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Inui
Naoki
N
Morita
Hiroshi
H
Takeuchi
Kazuhiko
K
Uchida
Shinya
S
Watanabe
Hiroshi
H
Nakamura
Hirotoshi
H
D000328:Adult; D065692:Cytochrome P-450 CYP3A Inhibitors; D004347:Drug Interactions; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000652:urine; D008297:Male; D008874:Midazolam / Q000493:pharmacokinetics*; D008875:Middle Aged; D013963:Thyroid Hormones / Q000009:adverse effects*; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000009:adverse effects*
D065692:Cytochrome P-450 CYP3A Inhibitors; D013963:Thyroid Hormones; D014284:Triiodothyronine; C001380:6 beta-hydroxycortisol; D013972:Thyrotropin; D013974:Thyroxine; D008874:Midazolam; D006854:Hydrocortisone