The effect of ketoconazole and diltiazem on oestrogen metabolism in postmenopausal women after single dose oestradiol treatment.
OBJECTIVE
The effect of the CYP3A4 inhibitors ketoconazole and diltiazem on the pharmacokinetics of oestrone was studied in six healthy postmenopausal women after treatment with a single oral dose of oestradiol.


METHODS
Plasma oestrone concentrations were measured following the administration of 1) oestradiol, 2) oestradiol and ketoconazole and 3) oestradiol and diltiazem.


RESULTS
Treatment with ketoconazole increased the AUC of oestrone (+ 4029 nmol l-1 h; 95% CI on the difference: 1588, 6471) and its Cmax (+ 306 nmol l-1; 95% CI on the difference: 117, 496). The AUC and Cmax of oestrone tended to increase on treatment with diltiazem although this did not reach the level of statistical significance.


CONCLUSIONS
The small increase in the plasma concentrations of oestrone formed from 17beta-oestradiol during co-administration with ketoconazole is unlikely to be clinically significant.
Annas
Anita
A
Department of Laboratory Medicine, Division of Clinical Pharmacology Karolinska Institutet at Huddinge University Hospital, 141 86 Stockholm, Sweden.
Carlström
Kjell
K
Alván
Gunnar
G
AL-Shurbaji
Ayman
A
D000284:Administration, Oral; D000935:Antifungal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D004110:Diltiazem / Q000008:administration & dosage / Q000494:pharmacology*; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D004967:Estrogens / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007654:Ketoconazole / Q000008:administration & dosage / Q000494:pharmacology*; D008875:Middle Aged; D017698:Postmenopause / Q000378:metabolism*
D000935:Antifungal Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D004967:Estrogens; D004958:Estradiol; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D004110:Diltiazem; D007654:Ketoconazole