Nine healthy male subjects and recreational users of 3,4-methylenedioxymethamphetamine (MDMA) participated in a study aimed to assess the usefulness of sweat testing for the detection of MDMA after a single 100-mg dose. Sweat was collected for up to 24 h with the PharmChek sweat patches from which drugs were eluted and then analyzed by immunoassay and gas chromatography-mass spectrometry using deuterated internal standards. The usefulness of a rapid onsite test, the Drugwipe immunochemical strip test, was also assessed. In the sweat patches, MDMA was detected as early as 1.5 h after consumption and peaked at 24 h. Intersubject variability was large; peak MDMA concentrations for the same dose varied in magnitude 30-fold. MDMA concentrations ranged between 3.2 and 1326.1 ng/patch. Only traces of the minor metabolite 3,4-methylenedioxyamphetamine were detected. In all subjects, the onsite test with the Drugwipe was positive at 1.5 h (peak time of MDMA plasma concentration). However, few false-negative results (18%) appeared in the first 6 h after administration. Both sweat patch testing and the onsite sweat strip test may find useful application for noninvasive monitoring of MDMA abuse in sweat.

An international collaborative study was undertaken involving 6 working groups to correlate the zone sizes obtained with 50 micrograms fosfomycin + 25 micrograms glucose-6-micrograms glucose-6-phosphate (G6P) and 50 micrograms fosfomycin + 50 micrograms G6P/disc with the MICs in the presence of 25 mg G6P/litre. The recommendations of the ICS for the MIC and disc diffusion methods were followed and Oxoid Mueller-Hinton agar was used. The regression lines obtained with the method of least squares show that the best correlation coefficient (r = 0.8227) corresponds to the disc with 50 micrograms fosfomycin + 50 micrograms G6P. Considering both the pharmacokinetics of fosfomycin after intravenous administration of 2 or 4 g and the distribution of sensitive bacterial populations, two breakpoints were established at MIC values of 16 and 64 mg/l corresponding to zone sizes and 18 and 22 mm, respectively.

Consumption of amfetamine-type stimulants, including classical amfetamines and 'designer drugs', has been recognised as one of the most significant trends in drug abuse at the end of the past century and at the beginning of the current one. The first cause is the increasing consumption amongst youth of methylenedioxy- and methoxy-substituted amfetamines, of which the pharmacology in humans is currently under investigation. Secondly, the abuse of more classical amfetamines, such as amfetamine itself and metamfetamine, continues to be highly prevalent in some geographical regions. Amfetamines are powerful psychostimulants, producing increased alertness, wakefulness, insomnia, energy and self-confidence in association with decreased fatigue and appetite as well as enhanced mood, well-being and euphoria. From a clinical pharmacokinetic perspective, amfetamine-type stimulants are rather homogeneous. Their oral bioavailability is good, with a high distribution volume (4 L/kg) and low binding to plasma proteins (less than 20%). The elimination half-life is 6-12 hours. Both hepatic and renal clearance contribute to their elimination from the body. Hepatic metabolism is extensive in most cases, but a significant percentage of the drug always remains unaltered. Amfetamine and related compounds are weak bases, with a pKa around 9.9, and a relatively low molecular weight. These characteristics allow amfetamine-type stimulants to diffuse easily across cell membranes and lipid layers and to those tissues or biological substrates with a more acidic pH than blood, facilitating their detection in alternative matrices at relatively high concentrations. In most cases, the concentrations found are higher than expected from the Henderson-Hasselbach equation. Drug monitoring in non-conventional biological matrices (e.g. saliva, hair, nails, sweat) has recently gained much attention because of its possible applications in clinical and forensic toxicology. An individual's past history of medication, compliance or drug abuse can be obtained from testing of hair and nails, whereas data on current status of drug use can be provided by analysis of sweat and saliva. Because of the physicochemical properties of amfetamine-type stimulants, this group of drugs is one of the most suitable for drug testing in non-conventional matrices.

A simulation study was performed to evaluate and compare the standard dosage regimen of 250 mg/12 h versus 500 mg/24 h of ciprofloxacin for the treatment of urinary tract infections (UTIs). Pharmacokinetic parameters reported for healthy young and old individuals were used for the simulation of drug levels in urine, at different mean urine flow rates (1-2.5 L/day). Pharmacokinetic/pharmacodynamic analysis of the results revealed that 500 mg ciprofloxacin once a day produced a more favourable profile in urine than 250 mg/12 h, particularly in the elderly, due to the slower elimination of the drug in this group of patients. Circadian rhythms were also considered for the simulation of drug levels in urine. According to the results, 500 mg once a day administered in the morning would be a better choice than 250 mg/12 h at least for uncomplicated UTI; nevertheless, clinical assays are needed to prove this hypothesis.

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