LIQUID-PHASE MICROEXTRACTION FOR SIMULTANEOUS CHROMATOGRAPHIC ANALYSIS OF THREE ANTIDEPRESSANT DRUGS IN PLASMA

A method using Liquid Phase Microextraction for simultaneous detection of citalopram (CIT), paroxetine (PAR) and fluoxetine (FLU), using venlafaxine as internal standard, in plasma by high performance liquid chromatography with fluorescence detection was developed. The linearity was evaluated between 5.0 and 500 ng mL(-1) (r > 0.99) and the limit of quantification was 2.0, 3.0 and 5.0 ng mL-1 for CIT. PAR and FLU, respectively. Therefore, it can be applied to therapeutic drug monitoring, pharmacokinetics or bioavailability studies and its advantages are that it necessary relatively inexpensive equipment and sample preparation techniques.

Determination of anticonvulsants in human plasma using SPME in a heated interface coupled online to liquid chromatography (SPME-LC)

A simple and sensitive method using solid phase microextraction (SPME) and liquid chromatography (LC) with heated online desorption (SPME-LC) was developed and validated to analyze anticonvulsants (AEDs) in human plasma samples. A heated lab-made interface chamber was used in the desorption procedure, which allowed the transference of the whole extracted sample. The SPME conditions were optimized by applying an experimental design. Important factors are discussed such as fiber coating types, pH, extraction time and desorption conditions. The drugs were analyzed by LC, using a C18 column (150 mm x 4.6 mm x 5 mm); and 50 mmol L-1, pH 5.50 ammonium acetate buffer : acetonitrile : methanol (55 : 22 : 23 v/v) as the mobile phase with a flow rate of 0.8 mL min(-1). The suggested method presented precision (intra-assay and inter-assay), linearity and limit of quantification (LOQ) all adequate for the therapeutic drug monitoring (TDM) of AEDs in plasma.

Diminished Mycophenolic Acid Exposure Caused by Omeprazole May Be Clinically Relevant in the First Week Posttransplantation

Background: Some studies have reported a decreased absorption of mycophenolic acid (MPA) from mycophenolate mofetil (MMF) in renal transplanted (RTx) patients under proton-pump inhibitors (PPIs). There is still a lack of information regarding (1) whether this effect occurs when MMF is administered with either tacrolimus or cyclosporine A [calcineurin inhibitors (CNIs)], (2) whether the effect has the same amplitude during the first year after RTx, and finally (3) whether this decrease in exposure is clinically relevant. Methods: We retrospectively analyzed the omeprazole effect in 348 12-hour pharmacokinetic samplings [area under the curve (AUC) 0-12h] performed on days 7, 14, 30, 60, 180, and 360 after RTx in 77 patients who participated in previous trials. Results: For all periods, the groups with and without PPI did not differ in all variables. By mixed-model analysis of variance, PPI reduced the MPA AUC(0-12h) (P < 0.0008) in the patients under both CNIs mainly due to decreased absorption (P = 0.049). In the tacrolimus group, a lower exposure seemed also due to a decreased MPA reabsorption at 10-12 hours. The PPI effect remains throughout the first year but was clinically more important on day 7. By Cox analysis, the use of PPI was associated with a 25% less chance of being adequately exposed to MPA (95% confidence interval 0.58-0.99, P = 0.04). Similarly, the number of patients underexposed to MPA (AUC < 30 ng.h/mL) was higher at most periods in the PPI group but again not statistically significant. Conclusions: These data indicate that PPI decreases the MPA exposure when associated with both CNIs but particularly in the first week after RTx. In this period, the MMF dose should be increased. This effect lasts throughout the first year but does not seem to be clinically relevant after the first week.

Liquid-phase microextraction for simultaneous chromatographic analysis of three antidepressant drugs in plasma

A method using Liquid Phase Microextraction for simultaneous detection of citalopram (CIT), paroxetine (PAR) and fluoxetine (FLU), using venlafaxine as internal standard, in plasma by high performance liquid chromatography with fluorescence detection was developed. The linearity was evaluated between 5.0 and 500 ng mL-1 (r > 0.99) and the limit of quantification was 2.0, 3.0 and 5.0 ng mL-1 for CIT, PAR and FLU, respectively. Therefore, it can be applied to therapeutic drug monitoring, pharmacokinetics or bioavailability studies and its advantages are that it necessary relatively inexpensive equipment and sample preparation techniques.

Monitoring Drug Use Among HIV/AIDS Patients in Brazil: Should we Combine Self-Report and Urinalysis?

Illicit drug use in HIV-infected patients can be linked to impairment of physical and mental health, low health-related quality of life, and suboptimal adherence to HIV treatment. This study aimed to evaluate the correlation of self-report illicit drug use, urinalysis for cocaine and cannabis metabolites, and severity of dependence among HIV-infected patients on antiretroviral therapy (ART) in a treatment center in Brazil. Four hundred and thirty-eight outpatients of an HIV referral center were interviewed and assessed for drug use (lifetime, last year and last month). Urinalysis was performed to detect the presence of cocaine and cannabis metabolites in urine samples. Overall agreement between self-report and urinalysis was almost 68% for cannabis and higher than 85% for cocaine. Positive urinalysis was significantly associated with more than once a week cannabis (p < .0001) and cocaine (p <.0001) use during the last-month. Severity of Dependence Scale (SDS) properly predicted positive cocaine urinalysis results (area under the curve [AUC] = .81, p = .0001). Frequency of cannabis and cocaine use, SDS score degree and positive urinalysis for both drugs were correlated. Our findings suggest that positive self-report is a reliable predictor of positive urine sample both for cannabis and cocaine, but since the agreement was not perfect, there is a role for urine drug screening in the care of patients with HIV-related conditions.

A New Method to Predict the Epidemiology of Fungal Keratitis by Monitoring the Sales Distribution of Antifungal Eye Drops in Brazil

Purpose: Fungi are a major cause of keratitis, although few medications are licensed for their treatment. The aim of this study is to observe the variation in commercialisation of antifungal eye drops, and to predict the seasonal distribution of fungal keratitis in Brazil. Methods: Data from a retrospective study of antifungal eye drops sales from the only pharmaceutical ophthalmologic laboratory, authorized to dispense them in Brazil (Opthalmos) were gathered. These data were correlated with geographic and seasonal distribution of fungal keratitis in Brazil between July 2002 and June 2008. Results: A total of 26,087 antifungal eye drop units were sold, with a mean of 2.3 per patient. There was significant variation in antifungal sales during the year (p < 0.01). A linear regression model displayed a significant association between reduced relative humidity and antifungal drug sales (R-2 = 0.17, p < 0.01). Conclusions: Antifungal eye drops sales suggest that there is a seasonal distribution of fungal keratitis. A possible interpretation is that the third quarter of the year (a period when the climate is drier), when agricultural activity is more intense in Brazil, suggests a correlation with a higher incidence of fungal keratitis. A similar model could be applied to other diseases, that are managed with unique, or few, and monitorable medications to predict epidemiological aspects.