[Study of effectiveness of craving control with topiramate in patients with substance dependence disorders]. / Estudio de la efectividad del control del craving con topiramato en pacientes con trastornos por dependencia de sustancias.

INTRODUCTION: Effectiveness and tolerability of topiramate at 3 and 6 months was assessed in patients requesting dehabituation programs. METHODS: Observational, prospective, national and multicenter study of 6 months, in patients on treatment with topiramate, who fulfilled criteria for dependence of opiates according to ICD-10 participating in therapeutic programs of dehabituation, without concomitant psychiatric illnesses and any responsible relative. Main measures of effectiveness were retention rates, alcohol consumption and other illicit drugs by urine tests (opiates, cannabis, cocaine) and treatment needs by EuropASI scale. Other parameters were HAM-D, DAS-SV and SF-36. RESULTS: Patients with consumption by urine tests decreased from 94.1 % (n = 64) at baseline to 39.6 % (n = 19) after 6 months of treatment, as was seen by means of the mean score in EuropASI scale, for all substances except methadone. No consumption was accompanied by a low rate of relapse of 33.3 % at 6 months. Twenty one patients had adverse reactions (28 %). The most frequent adverse reactions were somnolence (n = 9; 12 %), paraesthesia (n = 5; 6.7 %) and depression (n = 4; 5.3 %). CONCLUSIONS: In real clinical practice, topiramate showed a good response with a relevant decrease of percent of patients with abuse or consumption, and a satisfactory tolerability profile for the treatment of patients with dependence on heroine, cocaine, and other opiates, showing better outcomes than those obtained in previous trials.

A capillary gas chromatographic assay with nitrogen phosphorus detection for the quantification of topiramate in human plasma, urine and whole blood.

An accurate and robust method involving liquid liquid extraction and capillary gas chromatographic (GC) assay with nitrogen phosphorus detection (NPD) was developed and validated for the quantitative determination of topiramate [2,3:4,5-bis-O-(-1-methylethylidene)-beta-D-fructopyranose sulfamate], Topamax, an anticonvulsant drug, in human plasma, urine, and whole blood. The galactopyranose analog of topiramate was used as the internal standard. A DB-5, fused silica capillary column (J&W Scientific, Folsom, CA) was used, yielding typical retention times of 4.95 min for topiramate and 5.32 min for the internal standard in human plasma. The assay involved organic extraction with methyl t-butyl ether (MTBE) from base, a back extraction into acid and a second extraction in MTBE. The organic solvent was evaporated, and the residue was redissolved and injected for analysis. The standard curve was validated from 0.5 to 50 microg/ml(-1) for human plasma and whole blood, and from 1.0 to 50 microg/ml(-1) for urine. Peak area ratios of drug to internal standard were determined and used to construct a standard curve. The resulting chromatograms showed no endogenous interfering peaks with the respective blank human fluids. Chromatograms corresponding to topiramate and the internal standard produced sharp peaks that were well resolved. This assay showed precision and accuracy of < or = 5%. Two minor human metabolites of topiramate did not interfere with the assay. This assay was successfully applied to determine the pharmacokinetics of topiramate during the development of this drug.

Effect of maternal glucocorticoid treatment on ovine fetal fluids at 0.6 gestation.

This study examined the effects of maternal dexamethasone treatment on the volume and composition of fetal fluids, and on placental morphology at 0.6 gestation (80-90 days). Nine pregnant ewes were infused with dexamethasone (D, 0.76 mg h-1 for 72 h) while an additional nine ewes received saline (S, 0.38 mL h-1 for 72 h). Allantoic fluid (ALF) volume was significantly greater (P < 0.01) in the D group (737 +/- 116 mL) than in the S group (190 +/- 55 mL), but there was no difference in amniotic fluid (AMF) volume. The urine flow rate was 11 times higher in three D fetuses. The 51Cr-EDTA infused into the bladders of four fetuses during the final 4-5 h of the 72 infusions was detected in both AMF and ALF. Dexamethasone treatment significantly altered the composition of the fetal fluids but had no affect on fetal body weight, organ weights and placental weight; however, there were fewer cotyledons under 5 g (P < 0.05). In the D group, 3% of cotyledons were of the 'bovine' type in morphology, whereas all cotyledons in the S group were of the 'ovine' type. These findings suggest that prolonged exposure to large doses of glucocorticoids during pregnancy would affect the volume and composition of the fetal fluids and placental morphology, with potentially detrimental effects on the fetus.