Objective: Therapeutic drug monitoring (TDM) of the new generation antidepressants is subject of controversial discussion. Nonetheless, TDM may safeguard against drug-drug interactions, can be used to control compliance and is valuable in the investigation of overdose. Method: The aim of this prospective study was to investigate serum levels of trazodone when prescribed as monotherapy or when used in combination with the selective serotonin reuptake inhibitors citalopram and fluoxetine in a simultaneous assay using high-performance liquid chromatography (HPLC). Over a 1-year period, we studied 97 patients (63 females) with depressive syndrome who were subdivided into 3 main diagnostic groups. Fifty-two patients were smokers, the mean age was 39.9 years and the mean weight was 72.4 kg; 40 patients were taking trazodone alone, 41 trazodone in combination with citalopram and 16 patients trazodone in combination with fluoxetine. Results: The use of citalopram and fluoxetine in combination with trazodone had no significant impact on trazodone serum levels, and the same was true for differences in body weight and smoking behavior. On the other hand, age and sex had a significant influence on the pharmacokinetic pattern of trazodone, causing higher concentrations in females and in older patients. Since the polypharmacy investigated did not change the serum levels of trazodone, we assume that there is no metabolic interaction between trazodone and citalopram and trazodone and fluoxetine. We observed none of the adverse effects which might have been expected, including dizziness, severe headache, daytime sedation, fatigue or the serotonin syndrome even in a mild form. Conclusion: A "double-tracked" antidepressive treatment using trazodone and the SSRIs citalopram and fluoxetine is associated with a wide safety margin.

We describe an isocratic reversed-phase liquid chromatographic method for the determination of venlafaxine (VLX) and its main active metabolite O-desmethylvenlafaxine (ODV) in serum, using haloperidol as internal standard and liquid/liquid extraction for sample preparation. VLX and ODV were separated on a C18 column with a mobile phase of acetonitrile/buffer (30/70, v:v) at 60 degrees C and a flow rate of 1.5 ml/min. The measurement of the native fluorescence signals of the eluted compounds were carried out at 227/300 nm (excitation/emission) without interference from endogenous components in serum. High linearities for VLX and ODV for concentrations between 20 and 500 microg/l were obtained (r = 0.9997). A large spectrum of routinely prescribed drugs did not interfere in the assay. The coefficients of variation for repeatability varied between 5.40% and 5.99% and for reproducibility between 9.43% and 21.63%. Absolute recoveries were more than 52% for both substances.

We describe an analytical procedure for the simultaneous quantification of citalopram (seropram), clozapine (leponex), fluoxetine (fluctine), norfluoxetine, maprotiline (ludiomil), desmethylmaprotiline and trazodone (trittico) in human serum within a period of 11.5 minutes using reversed phase HPLC. After 2 liquid/liquid extractions in the sample preparation phase, the drugs and metabolites were separated on a C18 column using a mobile phase consisting of acetonitrile/buffer (30/70, v:v) at 70 degrees C, a flow rate of 1.5 m/min and haloperidol as internal standard. Absorption and native fluorescence signals of the eluted compounds were detected simultaneously at 260 nm and 227/300 nm (excitation/emission), respectively. The calibration ranges for citalopram, clozapine, fluoxetine, norfluoxetine, maprotiline, and desmethylmaprotiline ranged from 50-400 microg/l and for trazodone from 50-3,200 microg/l. The CVs varied between 0.6% and 5.5% (within-run) and between 3.2% and 7.1% (between-run). Recoveries were > 90% for all pharmaceuticals. We noticed no interferences from several commonly used drugs.

s: Fourth International Congress of Therapeutic Drug Monitoring and Clinical Toxicology Vienna, Austria September 4–8, 1995: Poster Session I: Clinical Toxicology/Therapeutic Drug Monitoring: PDF Only