title: An evaluation of the potential for pharmacokinetic interaction between escitalopram and the cytochrome P450 3A4 inhibitor ritonavir.
abstract: BACKGROUND
  Depression often coexists with a number of disease states, and patients with a diagnosis of depression often receive multiple medications. Thus, it is desirable to avoid coadministration of agents that have a potential for drug interactions in these patients. Although escitalopram and its metabolites are weak to negligible inhibitors of the cytochrome P450 (CYP) 3A4 isozyme and are therefore unlikely to affect plasma concentrations of ritonavir (a CYP3A4 substrate and prototype CYP3A4 inhibitor), ritonavir may potentially affect plasma concentrations of escitalopram, as CYP3A4 is partially responsible for conversion of escitalopram to its major metabolite, S-demethylcitalopram (S-DCT).
  
  
  OBJECTIVE
  The aim of this study was to investigate the potential for pharmacokinetic interaction between escitalopram and ritonavir after concomitant administration of a single dose of each in healthy young subjects.
  
  
  METHODS
  In this single-center, randomized, open-label, 3-way crossover study, subjects received each of the following: a single dose of escitalopram 20 mg, a single dose of ritonavir 600 mg, and single doses of both escitalopram 20 mg and ritonavir 600 mg. Blood was collected and plasma was analyzed for the pharmacokinetic parameters (maximum plasma concentration [C(max)], time to C(max) [T(max)], area under the plasma concentration-time curve, plasma elimination half-life, oral clearance, and apparent volume of distribution) of escitalopram, S-DCT, and ritonavir.
  
  
  RESULTS
  Of 21 subjects (11 men, 10 women; mean [SD] age, 28.4 [4.4] years) who were enrolled, 18 completed the study. After concomitant administration of escitalopram and ritonavir, no statistically significant differences were noted in the pharmacokinetics of escitalopram, with the exception of apparent volume of distribution, which was reduced by approximately 10% (P < 0.001). The pharmacokinetics of S-DCT were unaffected by coadministration of ritonavir, with the exception of T(max), which was increased in the presence of ritonavir. The pharmacokinetic parameters of ritonavir were also unaffected by coadministration of escitalopram.
  
  
  CONCLUSIONS
  In general, no pharmacokinetic interaction was observed between escitalopram and ritonavir in the present study.
authors.affiliation: Forest Laboratories, Inc., New York, New York, USA. Marcello.Gutierrez@frx.com
authors.forename: Marcelo M
authors.initials: MM
authors.lastname: Gutierrez
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Rosenberg
authors.forename: Wattanaporn
authors.initials: W
authors.lastname: Abramowitz
mesh_terms: D000293:Adolescent; D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D015283:Citalopram / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D019438:Ritonavir / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D018687:Antidepressive Agents, Second-Generation; D065607:Cytochrome P-450 Enzyme Inhibitors; D017320:HIV Protease Inhibitors; D015283:Citalopram; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D019438:Ritonavir