title: Pharmacokinetic drug-drug interaction study between raltegravir and citalopram.
abstract: Depression is the most common mental health disorder among HIV-infected patients. When treating HIV-infected patients with a selective serotonin reuptake inhibitor (SSRI), potential drug-drug interactions with antiretroviral agents have to be taken into account. We investigated the two-way pharmacokinetic drug-drug interaction and tolerability of concomitant administration of the SSRI citalopram and the HIV-1 integrase inhibitor raltegravir in healthy volunteers.
  
  
  
  An open-label, crossover, two-period trial was conducted in 24 healthy volunteers. Subjects received the following treatments: citalopram 20 mg once daily for 2 weeks followed by the combination with raltegravir 400 mg twice daily for 5 days and after a washout period raltegravir 400 mg twice daily for 5 days. Intensive steady-state pharmacokinetic blood sampling was performed. Geometric mean ratios (GMRs) of the combination versus the reference treatment and 90% CIs were calculated for the area under the plasma concentration-time curve (AUC). CYP2C19 genotyping was performed because it influences N-demethylation of citalopram to desmethylcitalopram.
  
  
  
  A total of 22 healthy volunteers completed the trial. GMRs (90% CI) were 1.00 (0.98, 1.03) for citalopram AUC0-24 h, 0.99 (0.88, 1.12) for desmethylcitalopram AUC0-24 h and 0.77 (0.50, 1.19) for raltegravir AUC0-12 h. Raltegravir plasma concentration 12 h after intake (C12 h) did not change with concomitant use of citalopram. Within each CYP2C19 phenotype subgroup the citalopram metabolite-to-parent ratio, which is a measure for metabolic enzyme activity, was not influenced by concomitant raltegravir use.
  
  
  
  Raltegravir does not influence the pharmacokinetics of citalopram and desmethylcitalopram. Citalopram did not change the pharmacokinetics of raltegravir in a clinically meaningful way. The combination was well tolerated and can be administered without dose adjustments. ClinicalTrials.gov NCT01978782.
authors.affiliation: Department of Pharmacy, Radboud university medical center, Nijmegen, the Netherlands. Maren.Blonk@radboudumc.nl.
authors.forename: Maren I
authors.initials: MI
authors.lastname: Blonk
authors.forename: Charlotte Ca
authors.initials: CC
authors.lastname: Langemeijer
authors.forename: Angela Ph
authors.initials: AP
authors.lastname: Colbers
authors.forename: Karin Ej
authors.initials: KE
authors.lastname: Hoogtanders
authors.forename: Ron Hn
authors.initials: RH
authors.lastname: van Schaik
authors.forename: Bas Jjw
authors.initials: BJ
authors.lastname: Schouwenberg
authors.forename: David M
authors.initials: DM
authors.lastname: Burger
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D015283:Citalopram / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018592:Cross-Over Studies; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics; D004347:Drug Interactions; D005260:Female; D005838:Genotype; D006207:Half-Life; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D008297:Male; D010641:Phenotype; D000068898:Raltegravir Potassium / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D015283:Citalopram; D065731:Cytochrome P-450 CYP2C19; D000068898:Raltegravir Potassium; D017367:Selective Serotonin Reuptake Inhibitors