Effect of cyamemazine on the steady-state plasma concentrations of risperidone and 9-hydroxyrisperidone: a preliminary retrospective study.

Administration of cyamemazine, an antipsychotic drug with anxiolytic properties, together with other antipsychotic agents is common in patients with schizophrenia. This retrospective study investigated the effects of cyamemazine on the steady-state plasma concentrations of risperidone and 9-hydroxyrisperidone in 47 patients treated with 1 to 12 mg/day of risperidone. Of these 47 patients, 24 were receiving cyamemazine comedication ("cyamemazine" group) and 23 patients were treated with risperidone alone ("control" group). Plasma concentrations were measured using a high-performance liquid chromatographic method with photodiode-array ultraviolet detection. The median plasma concentration of risperidone was significantly higher in the cyamemazine group (31.5 ng/mL) than in the control group (5.0 ng/mL), whereas the 9-hydroxyrisperidone median concentration was significantly lower in the cyamemazine group (16.5 ng/mL versus 39.0 ng/mL in the control group). However, the sum of risperidone plus 9-hydroxyrisperidone (active moiety) plasma concentration was not significantly affected by cyamemazine comedication. A combination with cyamemazine resulted in an inverted metabolic ratio (risperidone/9-hydroxyrisperidone). These findings suggest that cyamemazine inhibits the 9-hydroxylation of risperidone and is probably an inhibitor of cytochrome P450 2D6 as are many other phenothiazine drugs.

Development and validation of a high-performance liquid chromatography method using diode array detection for the simultaneous quantification of aripiprazole and dehydro-aripiprazole in human plasma.

A high-performance liquid chromatography method with diode array detection (HPLC-DAD) was developed for quantification of aripiprazole and dehydro-aripiprazole, in human plasma. After a simple liquid-liquid extraction, chromatographic separation was carried out on a C18 reversed-phase column, using an ammonium buffer-acetonitrile mobile phase (40:60, v/v). The total run time was only 7 min at a flow-rate of 1.0 ml/min. The precision values were less than 12% and the accuracy values were ranging from 98 to 113% and the lower limit of quantification was 2 ng/ml for both compounds. Calibration curves were linear over a range of 2-1000 ng/ml. The mean trough plasma concentrations in patients treated with aripiprazole were 157 and 29 ng/ml for aripiprazole and dehydro-aripiprazole, respectively.

Association of CK19 mRNA detection of occult cancer cells in mediastinal lymph nodes in non-small cell lung carcinoma and high risk of early recurrence.

This study was designed to screen occult cancer cells by CK19 mRNA detection using reverse transcriptase-polymerase chain reaction (RT-PCR) in mediastinal lymph nodes stations (MLNS) in non-small cell lung carcinoma (NSCLC). In 49 NSCLC patients free of mediastinal adenopathy on computed tomograph, 254 MLNS were evaluated by histopathology, immunohistochemistry (IHC) and RT-PCR. Of 225 non-tumoral MLNS on histopathology, 32 (14.2%) were positive by RT-PCR. IHC did not provide significant additional results. Seventeen patients were without mediastinal tumoral extension on histopathology and RT-PCR (Group 1), 16 were upgraded by RT-PCR (Group 2) and 16 pN2 on histopathology (Group 3). The two-year cancer-related death survival in Groups 1 (100%) and 2 (64.5%) was significantly different (P=0.04). The relative risk of recurrence in Group 2 compared with Group 1, evaluated by the Cox model multivariate analysis, was 5.61 (P=0.02). In conclusion, CK19 mRNA detected by RT-PCR in MLNS was significantly associated with an increased risk of rapid recurrence.

Antidepressant agents in short bowel syndrome.

PURPOSE: This study aimed to determine whether short small intestine modifies antidepressant concentrations. METHODS: The Css values and concentration-dose ratios (CDRs) of citalopram or escitalopram, administered orally or intravenously, were determined in patients with short bowel syndrome. FINDINGS: Eight patients (6 males and 2 females) were included in the study. High CDRs were obtained in orally treated patients with >180 cm of small bowel and in those with >80 cm of small bowel and 50% of colon. Three patients had low Css values, including 1 patient who received intravenous treatment. IMPLICATIONS: The variability of drug absorption and metabolism makes prescribing SSRIs challenging in these patients.

Therapeutic drug monitoring of levetiracetam by high-performance liquid chromatography with photodiode array ultraviolet detection: preliminary observations on correlation between plasma concentration and clinical response in patients with refractory epilepsy.

Levetiracetam is a new antiepileptic drug prescribed for the treatment of patients with refractory partial seizures with or without secondary generalization as well as for the treatment of juvenile myoclonic epilepsy. A rapid and specific method by high-performance liquid chromatography diode array detection was developed to measure the concentration of levetiracetam in human plasma. The trough plasma concentrations measured in 69 epileptic patients treated with 500 to 3000 mg/d of levetiracetam ranged from 1.1 to 33.5 microg/mL. The mean (range) levetiracetam plasma concentrations in responders and nonresponders were 12.9 microg/mL (4.6-21 microg/mL) and 9.5 microg/mL (1.1-20.9 microg/mL), respectively. A wide variability in concentration-response relationships was observed in patients. Using a receiver operating characteristic curve, the threshold levetiracetam concentration for a therapeutic response was 11 microg/mL. The sensitivity and specificity for this threshold levetiracetam concentration were 73% and 71%, respectively. According to chi analysis, this finding was not significant probably because of the small number of patients and because of their refractory seizure type. Nevertheless, the levetiracetam plasma concentration could be used to help clinicians detect severe intoxication or to verify compliance by repeating the measurement in patients.