Because protein binding is a process that can be changed by the presence of other drugs with similar or greater affinity for proteins than the original compound, this causes a greater concentration of the free drug, while potentializing adverse effects, the most important factor responsible for noncompliance (Demyttenaere 1997; Fincke et al. 1998). The purpose of this study was to measure the binding of imipramine to plasma proteins when administered simultaneously with acetyl salicylic acid (ASA). Such interaction would be more clearly defined using clinical assessment parameters in patients treated with imipramine, who additionally need the second drug. The study was carried out in 20 clinically diagnosed depressed patients (16 F, 4 M, average age 38.3 ± 13.3 years and weight 63.8 ± 9.0 kg) to which imipramine (Tofranil) was administered at doses of 75 mg every 12 h. Informed consent was obtained for all patients before the study.

After the first 3 days, while fasting, 6-ml blood samples were taken from the patients and processed. The following were measured: (1) total concentration of the drug in plasma; (2) fraction of imipramine bound to plasma proteins as reported in Juárez and Jung (1986), and protein levels, as indicators of the protein state in the patients studied. Before taking the sample, each patient's clinical state was assessed using a questionnaire on the possible effects a patient reported, recording the time when the effect arose, its duration, and its severity. This questionnaire was previously validated by the Mental Health Division, Department of the Faculty of Medicine (UNAM). After this first phase, patients took 500 mg of ASA every 12 h for 2 days. At this time, a second sample was taken. The samples were processed, and the parameters as above were assessed. Patients were asked to answer the questionnaire again. The adverse effects were registered and investigation proceedings were carried out by the psychiatry service medical staff at INNN, who had no information about the patients’ treatment. These professionals were well qualified to evaluate the described adverse effects.

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