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This study evaluates the suitability of gas chromatographic-mass spectrometric (GC-MS) analysis to follow-up the extent of benzodiazepine (mis)use in a Belgian prison population and compares it to other analytical strategies (e.g. screening followed by confirmation of the positive samples). From February to August 1998, 598 persons were jailed of which 188 (31.4% of the incoming detainees) volunteered to be screened. Urine samples (530 in total) were collected on the day of arrival and after 14, 30 and 90 days of imprisonment. All samples were screened by EMIT® for benzodiazepines and analysed subsequently by GC-MS. EMIT® screening yielded 117 (22.1%) positive samples, a number which increased to 174 (32.8%) after GC-MS analysis. Of these 174 GC-MS positive samples, 119 (68.4%) contained one benzodiazepine while for the remaining samples multiple benzodiazepine (mis)use could be demonstrated. A significant increase in benzodiazepine (mis)use was indicated only from day 0 to day 14 based on the GC-MS results but not on the immunoassay results, even when the latter were complemented with GC-MS analysis of the positively screened samples. The GC-MS data also demonstrated that benzodiazepines are mainly (mis)used by subjects on benzodiazepine prescription as almost 50% of these subjects took additional non-prescribed benzodiazepines. During GC-MS analysis other drugs were co-extracted unintentionally and chromatographed and 23.9% of the volunteers were positive for illegal drugs on the day of arrival. Immunoassay results yield an underestimation of the problem of benzodiazepine (mis)use in prison due to the high false negative rate. GC-MS analysis of all samples therefore is the recommended strategy for this type of longitudinal study as it yields more correct and detailed information than the immunoassay results. [ABSTRACT FROM AUTHOR]

Pregabalin, used for treating partial epilepsy and neuropathic pain, is usually well tolerated. Patients with impaired renal function are at risk to develop more serious adverse events. A 64-year-old woman was admitted in the Emergency Department for altered consciousness and abnormal movements. She recently started to take pregabalin (150 mg/day) for neuropathic pain. The drug was withdrawn 36 h before hospitalization following worsening of neurological symptoms. At physical examination, myoclonus was noted as main finding in the limbs and head, with encephalopathy. Laboratory investigations revealed acute renal failure with serum creatinine at 451.3 µmol/l. Urine output was preserved. After supportive care alone, myoclonus resolved after 24 h and consciousness was normal after 48 h. Renal function was also recovered. At the time of admission, the concentration of plasma pregabalin was 3.42 µg/ml, within therapeutic range. The calculated terminal elimination half?life was 11.5 h. Pregabalin-induced myoclonus may not be strictly related to drug accumulation in acute renal failure, with the possibility of a threshold phenomenon. [ABSTRACT FROM AUTHOR]

Background: Use of vitamin K antagonists for the prevention of stroke and systemic embolism in dialysis patients with nonvalvular atrial fibrillation is controversial. However, no good alternatives presently are available. The anti-factor Xa antagonist rivaroxaban is contraindicated for lack of pharmacokinetic, pharmacodynamic, and clinical data. This study aims to characterize the pharmacokinetics/pharmacodynamics of rivaroxaban in maintenance hemodialysis patients., Study Design: Pharmacokinetic and pharmacodynamic study., Setting & Participants: 18 maintenance hemodialysis patients without residual kidney function at 2 centers. DRUG ADMINISTRATION, OUTCOMES, & MEASUREMENTS: (1) A single dose of 10mg of rivaroxaban was administered at the end of each of 3 consecutive dialysis sessions and area under the curve (AUC) and the effect on coagulation parameters were measured for 44 hours thereafter. (2) A single dose of 10mg of rivaroxaban was given 6 to 8 hours before a dialysis session and the effect of dialysis on rivaroxaban concentrations was evaluated. (3) To assess potential accumulation, 10mg of rivaroxaban was given once daily and AUC was measured during 24 hours on days 1 and 7., Results: Mean AUC0-44 of rivaroxaban plasma concentrations after a single dose of 10mg was 2,072μg/L/h, mean maximum concentration was 172.6μg/L, and mean terminal elimination half-life was 8.6 hours. Dialysis had no appreciable effect on rivaroxaban plasma concentrations. Mean trough concentration after multiple daily doses of 10mg was 20.2μg/L., Limitations: Higher rivaroxaban doses and patients with substantial residual kidney function were not studied., Conclusions: A 10-mg dose of rivaroxaban in hemodialysis patients without residual kidney function results in drug exposure similar as published for 20mg in healthy volunteers. Rivaroxaban is not eliminated by dialysis. There is no accumulation after multiple daily dosing. The efficacy and safety of rivaroxaban in hemodialysis patients should be the subject of a large randomized trial., (Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Since vitamin C (ascorbic acid, AA) deficiency is common in hemodialysis patients, systematic supplementation has been recommended. Further, vitamin C has been advocated as a potential adjuvant to erythropoietin by virtue of its capacity to improve iron utilization. However, vitamin C may have a paradoxical pro-oxidant effect in the presence of iron., Methods: In 109 hemodialysis patients, oral vitamin C was administered at 360 and 1,500 mg/week during 3 months each, followed by a wash-out period of 3 months., Results: Serum AA increased from 0.22 to 0.33 and 0.63 mg/dl after 360 and 1,500 mg/week, respectively. However, a commensurate increase of plasma malondialdehyde (MDA), a parameter of lipid peroxidation, with 9 and 26% was observed. Serum AA and plasma MDA returned to baseline after withdrawal of vitamin C. Parameters of iron status, nutrition, inflammation, dialysis efficiency and plasma lipids remained unaltered. In a stepwise multiple regression analysis, serum AA and ferritin were strong and independent predictors of MDA., Conclusion: Oral vitamin C supplementation in hemodialysis patients increases lipid peroxidation, especially in patients with increased serum ferritin. The potential benefits of restored vitamin C status and improved erythropoiesis may be entirely overruled by the adverse consequences of oxidative tissue injury., ((c) 2007 S. Karger AG, Basel.)

Background: An accurate measurement of testosterone is needed in many clinical applications for correct diagnosis and appropriate treatment. Our aim was to develop a fast and robust high-throughput LC-MSMS method for quantification of serum testosterone in women., Methods: Testosterone was derivatized by oximation and extracted with methyl tert-butyl ether from 200 microL of serum. Further matrix elimination was achieved on-line using a column-switching LC-method. The instrumental analysis was performed on an API4000 tandem mass spectrometer equipped with an Agilent series 1312A binary pump and an Agilent series 1311A quaternary pump. The MRM transitions were 304-->124 and 304-->112 for testosterone and 307-->124 and 307-->112 for d(3)-testosterone., Results: The total analysis time of the column-switching method was 3 min. Linear calibration curves were obtained in the concentration range from 0.035 nmol/L (0.01 microg/L) to 6.92 nmol/L (2 microg/L). Within-day and between-day precision, expressed as the relative standard deviation at four different concentrations ranged from 4.70% to 9.35%. Correlation with the in-house method (solvent-extraction RIA) showed r(2)=0.920., Conclusions: The presented column-switching method offers a simple, fast and economical analysis of testosterone in human serum. The procedure requires only small sample volumes and is well suited for quantification of testosterone in serum from women and children.