Lack of Effect of a Single Dose of Ketoconazole on the Pharmacokinetics of Citalopram

STUDY OBJECTIVE: To determine whether the pharmacokinetics of the antidepressant citalopram are affected by ketoconazole, a potent inhibitor of cytochrome P450 (CYP) 3A4. DESIGN: Single-center, double-blind, randomized, three-way crossover trial. SETTING: Research facility. PARTICIPANTS: Eighteen healthy male and female volunteers. INTERVENTION: Subjects received three treatments with a 14-day washout period: single dose of ketoconazole 200 mg plus placebo, single dose of citalopram 40 mg plus placebo, and single dose of ketoconazole 200 mg plus single dose of citalopram 40 mg. MEASUREMENTS AND MAIN RESULTS: Pharmacokinetic parameters were determined after each treatment. The pharmacokinetic profile of citalopram administered alone was essentially identical to that when administered with ketoconazole. Similarly, the pharmacokinetics of the metabolite desmethylcitalopram were unaltered by ketoconazole. CONCLUSION: No changes in pharmacokinetics of citalopram were observed after coadministration of ketoconazole, suggesting that ketoconazole and other CYP3A4 inhibitors may be administered safely with citalopram. Furthermore, no adjustment of citalopram dosage should be necessary in most patients who receive the drug in combination with a CYP3A4 inhibitor.