The effect of ketoconazole and diltiazem on oestrogen metabolism in postmenopausal women after single dose oestradiol treatment

• Published in: British journal of clinical pharmacology Vol. 56; no. 3; pp. 334 - 336
• Main Authors: Annas, Anita, Carlström, Kjell, Alván, Gunnar, AL‐Shurbaji, Ayman
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.09.2003; Blackwell Science; Blackwell Science Inc
• Subjects: Administration, Oral; Antifungal Agents - administration & dosage; Antifungal Agents - pharmacology; Biological and medical sciences; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme Inhibitors; diltiazem; Diltiazem - administration & dosage; Diltiazem - pharmacology; Estradiol - administration & dosage; Estradiol - pharmacology; Estrogens - blood; Estrogens - pharmacokinetics; Female; Hormones. Endocrine system; Humans; ketoconazole; Ketoconazole - administration & dosage; Ketoconazole - pharmacology; Medical sciences; Medicin och hälsovetenskap; Middle Aged; oestradiol; oestrogen metabolism; Pharmacology. Drug treatments; postmenopausal; Postmenopause - metabolism; Short Reports; Antianginal agent; Imidazole derivatives; Coronary vasodilator agent; Isozyme; Calcium antagonist; Estrogen; oestrogen metabolism; Benzothiazepine derivatives; Estradiol; Antifungal agent; Postmenopause; Female; Drug interaction; Human; Drug combination; Ketoconazole; Cytochrome P450; Single dose; Oral administration; Enzyme inhibitor; oestradiol; Antiarrhythmic agent; Diltiazem; Metabolism; Sex steroid hormone; Pharmacokinetics; postmenopausal
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1046/j.1365-2125.2003.01885.x

Aims  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 17β‐oestradiol during co‐administration with ketoconazole is unlikely to be clinically significant.