In vitro effects of three antidepressant drugs on plasma paraoxonase activity.

BACKGROUND: Paraoxonase 1 (PON1) is important in organophosphates and xenobiotic metabolism and as an antioxidant bio-scavenger. PON1 activity was shown to significantly decrease in depressed patients after antidepressant treatment instauration. Our aim was to investigate the in vitro inhibitory effects of three antidepressants (imipramine, amitriptyline and fluoxetine) on PON1 activity. METHODS: Plasma from healthy volunteers was spiked with antidepressant drugs. The working solutions were then diluted with plasma to obtain concentrations that covered the therapeutic margin. PON1 was tested by a kinetic method in triplicate after incubation at 37°C for 2 h. RESULTS: Tricyclic antidepressants significantly inhibited PON1. Fluoxetine had no effect. The inhibition percentage for imipramine was 15.6% at 100 µg/L after incubation for 1 h (131±1 vs. 155±2 IU/L; p<0.01). At 350 µg/L, the inhibition percentage for imipramine 19.2% after 1 h and 20.2% after 2 h. Amitriptyline was a stronger inhibitor: 26% after 30 min at 125 µg/L. At 250 µg/L, the inhibition percentage for amitriptyline was 36.5% after 30 min (100±4 vs. 159±2 IU/L; p<0.01). CONCLUSIONS: The tested tricyclic antidepressants significantly inhibit PON1 activity in a concentration-dependent manner. Amitriptyline had a higher inhibition potency than imipramine.

Interference of tobacco smoke with immunochromatography assay for urinary drug detection.

BACKGROUND: This study aimed to evaluate the interference of tobacco smoke on immunochromatography assay of urinary drug detection. METHODS: Our study included 256 voluntary subjects (143 passive smokers and 113 current smokers). Cotinine was measured by immunoenzymatic method and thiocyanates (SCN(-)) by selective electrode. Urinary drug was detected by immunochromatography assay. A positive result is completed by an analytical method with an immunometric assay. RESULTS: False positive results for benzodiazepines are significantly more frequent in smokers compared with passive smokers (90.2% Vs 22.4%; χ(2) = 116.62, p < 10(-3)). For smokers, the number of cigarettes was significantly higher in subjects with falsely positive results for benzodiazepines compared with subjects with negative results (32 ± 11 Vs 20 ± 10; p = 0.04). Between these two groups, we established a significant difference for urinary cotinine (345 ± 211 Vs 117 ± 54 µg/µmol; p < 10(-3)) and for plasma SCN(-) (101.6 ± 3.4 Vs 98.8 ± 2.1 µmol/L; p = 10(-3)). Urinary cotinine and consumption duration present the highest values of areas under curves (AUC) of the receiver-operating-characteristic (ROC) curves. The cut-off of 167.6 µg/µmol and 10.5 years were found as predictive factors of false positive results. CONCLUSION: Tobacco smoke interferes with immunochromatography assay of urinary drug detection; therefore, all subjects must be questioned about their smoking status to avoid such false results during results interpretation.