| Publication Abstract Display | | Type: Poster | | Title: Low exposure to Paroxetine and Sertraline, but not to Citalopram, Escitalopram and Fluoxetine in HIV-infected patients. | | Authors: Best BM, Letendre S, Rossi S, Clifford D, Collier A, Gelman B, McArthur J, McCutchan J, Morgello S, Ellis R | | Date: 02-25-2007 | | Abstract:BACKGROUND. Antidepressants are widely prescribed to HIV-infected
individuals. Reduced efficacy and/or increased toxicity of selective serotonin
reuptake inhibitors (SSRIs) have been reported in some but not all studies of HIVinfected
patients. Excessively high or low exposure to SSRIs due to adherence,
drug-disease or drug-drug interactions may account for clinical differences between
individuals.
METHODS. 222 random SSRI concentrations at baseline and 6 month follow-up
visits (citalopram (C) = 61, escitalopram (E) = 49, fluoxetine (F) = 36, paroxetine
(P) = 29, sertraline (S) = 29) were measured by NPD capillary gas chromatography
from 161 HIV-infected participants (pts) of the CHARTER study, a North American
observational cohort. The POSTHOC Bayesian procedure in the software
NONMEM estimated the population predicted values for samples based on a onecompartment
model using published pharmacokinetic parameters. Individual
percentage of population predicted (%PP) concentrations were calculated and
compared using Kruskal-Wallis ANOVA on ranks.
RESULTS. Pts were mostly non-white (51%) men (68%) with a mean age of 43.7
years who were taking antiretrovirals (76%). Pts took SSRIs for 1.4 ± 2 years at
time of sample. Antiretroviral use, CD4 counts, and HIV RNA levels in CSF and
plasma did not differ between the groups defined by use of each of the 5 SSRIs.
Median (IQR) concentrations and times post-dose were as follows: C = 41 (15 –
96) ng/mL at 11.6 (4.7 – 18.5) hours; E = 14 (4 – 44) ng/mL at 7.2 (4.8 – 16) hours;
F = 20 (7 – 48) ng/mL at 7.7 (5.2 – 15.7) hours; P = 10 (3 – 20) ng/mL at 14.5 (6.4
– 17) hours; and S = 3 (0.1 – 14) ng/mL at 15.2 (6.3 – 23.1) hours. P and S
concentrations were significantly lower than expected (Median (IQR) %PP P = 0.2
(0.08 – 0.4) (p=0.003), S = 0.2 (0.005 – 0.4) (p=0.003)). Concentrations of C, E,
and F were similar to expected (Median (IQR) C = 0.6 (0.2 – 1.3), E = 0.5 (0.2 –
1.3), F = 0.8 (0.2 – 1.1), all p > .10).
CONCLUSIONS. In this observational cohort, concentrations of P and S – but not
C, E, and F – were significantly lower than those reported in pharmacokinetic
studies of HIV-uninfected depressed patients. Future studies to confirm these
observations, and to determine causative factors and clinical impact are needed. |
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