TY - JOUR
T1 - Pharmacokinetic drug-drug interaction study between raltegravir and citalopram
AU - Blonk, Maren I.
AU - Langemeijer, Charlotte C. A.
AU - Colbers, Angela P. H.
AU - Hoogtanders, Karin E. J.
AU - van Schaik, Ron H. N.
AU - Schouwenberg, Bas J. J. W.
PY - 2016
Y1 - 2016
N2 - Background: 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. Methods: 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. Results: A total of 22 healthy volunteers completed the trial. GMRs (90% CI) were 1.00 (0.98, 1.03) for citalopram AUC(0-24) (h), 0.99 (0.88, 1.12) for desmethylcitalopram AUC(0-24 h) and 0.77 (0.50, 1.19) for raltegravir AUC(0-12) (h). Raltegravir plasma concentration 12 h after intake (C-12 (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. Conclusions: 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.
AB - Background: 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. Methods: 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. Results: A total of 22 healthy volunteers completed the trial. GMRs (90% CI) were 1.00 (0.98, 1.03) for citalopram AUC(0-24) (h), 0.99 (0.88, 1.12) for desmethylcitalopram AUC(0-24 h) and 0.77 (0.50, 1.19) for raltegravir AUC(0-12) (h). Raltegravir plasma concentration 12 h after intake (C-12 (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. Conclusions: 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.
U2 - 10.3851/IMP2993
DO - 10.3851/IMP2993
M3 - Article
C2 - 26375942
SN - 1359-6535
VL - 21
SP - 143
EP - 152
JO - Antiviral Therapy
JF - Antiviral Therapy
IS - 2
ER -