Lack of effect of a single dose of ketoconazole on the pharmacokinetics of citalopram.
OBJECTIVE
To determine whether the pharmacokinetics of the antidepressant citalopram are affected by ketoconazole, a potent inhibitor of cytochrome P450 (CYP) 3A4.


METHODS
Single-center, double-blind, randomized, three-way crossover trial.


METHODS
Research facility.


METHODS
Eighteen healthy male and female volunteers.


METHODS
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.


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.


CONCLUSIONS
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.
Gutierrez
M
M
Department of Pharmacokinetics, Forest Laboratories, Inc., New York, New York 10022, USA.
Abramowitz
W
W
D000328:Adult; D000704:Analysis of Variance; D000935:Antifungal Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D015283:Citalopram / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007654:Ketoconazole / Q000493:pharmacokinetics*; D016014:Linear Models; D008297:Male; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000493:pharmacokinetics*
D000935:Antifungal Agents; D015283:Citalopram; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D007654:Ketoconazole; D006899:Mixed Function Oxygenases; D017367:Selective Serotonin Reuptake Inhibitors; C104464:CYP3A protein, human; C510163:CYP3A4 protein, human