Therapeutic drug monitoring of clomipramine and amitriptyline in a depressed patient with upper digestive tract resection.

We describe a 55-year-old woman with extensive digestive resection and recurrent depressive disorder resistant to oral clomipramine tablets but not to an oral solution of amitriptyline. In the light of this case report, the potential mechanisms of drug resistance after digestive resection are discussed, including the importance of drug monitoring.

Persistent high nevirapine blood level with DRESS syndrome 12 days after interruption of antiretroviral therapy.

Nevirapine is an antiretroviral agent associated with drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. Such a case in an immunocompetent woman recently treated with nevirapine for postexposure HIV prophylaxis is reported here. Despite a period of 12 days after interruption of treatment, a high blood level of nevirapine was still observed.

Reliability and validity of the French version of the tobacco craving questionnaire.

OBJECTIVES: (1) To assess the factorial structure, reliability and validity of the French language version of the Tobacco Craving Questionnaire (TCQ), a multidimensional, self-report instrument evaluating tobacco craving, to allow its use in French-speaking populations. (2) To compare the two different language versions of the same instrument in 2 independent samples from 2 cultures in 2 distinct time periods. METHODS: The French TCQ was administered to 226 current cigarette smokers after at least 2 h of abstinence. RESULTS: Despite the substantial difference in population characteristics between the French and American samples of smokers, both exploratory and confirmatory factor analyses indicated that the French version was best described by a 4-factor solution, similar to the original English version. Reliability estimates were 0.83, 0.79, 0.69 and 0.66 for the French and 0.82, 0.70, 0.75 and 0.48 for the English version for 'emotionality' (factor 1), 'expectancy' (factor 2), 'compulsivity' (factor 3) and 'purposefulness' (factor 4), respectively. The 4 factors accounted for 11.6, 17.1, 9.0, and 9.5% of the total variance in emotionality, expectancy, compulsivity, and purposefulness, respectively, for the French compared to 14.2, 12.5, 14.4 and 5% of the total variance for the English version, respectively. CONCLUSION: The French version of the TCQ is as valid and reliable instrument as the original English version and assesses the same 4 dimensions of craving for tobacco.

Effect of glucose on tobacco craving. Is it mediated by tryptophan and serotonin?

RATIONALE: Oral glucose has been shown to decrease tobacco craving in many but not all previous studies. Glucose ingestion may facilitates entry of tryptophan (TRP), the unique source of brain serotonin, into the brain, glucose's action seems to be opposite of rapid TRP depletion. Therefore, the aim was to assess the effect of high doses of oral glucose on tobacco craving, withdrawal symptoms, plasma TRP and blood serotonin concentrations in temporarily abstinent smokers. METHODS: Aspartame 0.6 g/200 ml (A, placebo), glucose 32.5 g/200 ml (G32.5) and 75 g/200 ml water (G75) were administered to 12 healthy smokers after an overnight abstinence in a crossover, double blind study. Tobacco craving (short version of the Tobacco Craving Questionnaire, TCQ), withdrawal symptoms, choice reaction time, affect, blood glucose, plasma insulin, nicotine, cotinine, free and total TRP, and blood serotonin concentrations were assessed during a period of 5 h after administration. RESULTS: Blood glucose and plasma insulin increased after G32.5, G75 and remained unchanged after A. TCQ score increased with A and remained almost unchanged with both doses of glucose (conditionxtime interaction: P=0.023). Total withdrawal score increased differently according to sex and condition (P<0.05). Motor reaction time increased with A and decreased with glucose (P=0.016). The overall decrease in plasma TRP was 0.31+/-17, 0.49+/-0.19 and 1.44+/-0.24 mg/l with A, G32.5 and G75, respectively (P<0.001). Baseline blood serotonin was lower in women (n=5) than in men; it showed a condition by time (P=0.007) and a condition by time by sex interaction (P=0.023). CONCLUSIONS: Glucose attenuates tobacco craving and withdrawal symptoms in temporarily abstinent smokers. This is accompanied by a decrease in plasma TRP and a sex dependent increase in blood serotonin. Further studies assessing the direct effect of glucose on brain serotonin are needed to ascertain whether a glucose induced reduction in craving is associated with an increase in brain serotonin.

Comparative pharmacokinetics and pharmacodynamics of intravenous and oral nefopam in healthy volunteers.

To determine the pharmacokinetic, subjective effects of a single 20 mg dose of nefopam administered either intravenously or orally in healthy volunteers, twenty-four healthy Caucasian men received 20 mg nefopam orally+placebo intravenous infusion and placebo orally+intravenous infusion of 20 mg nefopam with one week interval, in a double-blind, double-dummy cross-over study. Nefopam and desmethyl-nefopam plasma concentrations were measured by HPLC with UV detection up to 48 hr after drug administration. Self-rating questionnaires (Mood and vigilance Visual Analogue Scales, Addiction Research Centre Inventory) and drug safety were investigated. The F value (bioavailability) of the parent drug was 0.36+/-0.13. The AUCoral/AUCiv ratio of nefopam+desmethyl-nefopam was 0.62+/-0.23. The half-life of nefopam was similar whether administered orally (5.1+/-1.3 hr) or intravenously (5.1+/-0.6 hr). The half-life of desmethyl-nefopam was two to three times longer than that of the parent molecule (orally: 10.6+/-3.0 versus 5.1+/-1.3 hr, P<10(-4) and intravenously: 15.0+/-2.4 versus 5.1+/-0.6 hr, P<10(-4)). As assessed by the Addiction Research Centre Inventory, no evidence of abuse liability in healthy, drug-naive volunteers was observed. On visual analogue scales, volunteers rated themselves as more drowsy, less alert, less energetic and less anxious after oral compared to intravenous administration. The AUC0-->24 hr of anxiety and energy parameters were not different after oral and intravenous administration: 90+/-142 versus 35+/-84 (P=0.27) and 66+/-74 versus 46+/-54 mm x hr (P=0.36), respectively. The AUC0-->24 hr of drowsiness and alertness parameters were significantly greater after oral than after intravenous administration: 68+/-65 versus 27+/-30 (P=0.005) and 54+/-63 versus 28+/-48 mm x hr (P=0.03), respectively. A clockwise hysteresis loop was observed for drowsiness in 16 out of 24 volunteers after oral administration. The results suggest that in healthy volunteers desmethyl-nefopam may contribute to the pharmacodynamic effects of single dose nefopam solution administered orally. This study shows a rather low bioavailability of nefopam given in intravenous solution when administered orally. Nevertheless, when the main metabolite desmethyl-nefopam is taken into account, the ratio of the areas under the curves is almost doubled.

Amisulpride does not prevent relapse in primary alcohol dependence: results of a pilot randomized, placebo-controlled trial.

BACKGROUND: Few medications have been proved to be effective in preventing relapse in alcoholism. The mesolimbic dopamine system is known to play an important role in alcohol dependence. Amisulpride, a substituted benzamide, seems to facilitate dopaminergic neurotransmission at low doses. METHODS: After short-term, inpatient detoxification, 71 patients participated in a randomized, double-blind, placebo-controlled study to evaluate the efficacy of amisulpride in relapse prevention. Patients received amisulpride 50 mg/day or placebo for 6 months. RESULTS: There were no differences between the two groups of treatment for time to first drink, length of time before dropout, number of drinking days, and number of heavy drinking days. However, significantly more patients who were treated with amisulpride than those who were treated with placebo were nonabstinent and had relapsed at each visit. Craving for alcohol was significantly higher in the amisulpride than in the placebo group. Transaminases, gamma-glutamyl-transferase, and mean erythrocyte corpuscular volume were regularly higher in the amisulpride group than in the placebo group. CONCLUSIONS: The results indicate that treatment with amisulpride was not effective in preventing relapse to drinking in detoxified, alcohol-dependent patients. The significance of this finding is discussed, particularly in terms of the effects of neuroleptics on alcohol consumption.