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Marchei E.,Istituto Superiore di Sanita | Farre M.,University of the Sea | Pardo R.,University of the Sea | Garcia-Algar O.,Unitat de Recerca Infancia i Entorn URIE | And 3 more authors.
Therapeutic Drug Monitoring | Year: 2010

The pharmacokinetics of methylphenidate (MPH), a prescription amphetamine derivative used in the treatment of attention-deficit hyperactivity disorder, has been amply described in conventional biological matrices. Recently, the excretion of MPH and its principal metabolite, ritalinic acid (RA) in oral fluid and plasma after a single drug administration has been described. The aim of this study was to describe the excretion of MPH and RA in sweat after the administration of a single dose of either fast-release or extended-release MPH. Three male subjects received 2 simultaneous oral doses of 10 mg fast-release MPH, and 1 male subject received one dose of 20 mg extended-release MPH. Sweat patches were applied to the back of each participant and removed at timed intervals. MPH and RA were determined in patches using a previously validated liquid chromatography-electrospray ionization mass spectrometric method. MPH was detected in sweat after the administration of fast-and extended-release formulations. For the fast-release formulation, MPH appeared in the sweat patches 2 hours after administration with a maximum of 15.9 nanogram per patch, reached after 24 hours. Mean total MPH excreted was 0.02 mg (about 0.08% of the administered dose). For the extended-release formulation, MPH appeared in the sweat 5 hours after administration and reached a maximum of 34.3 nanogram per patch after 24 hours. Mean total MPH excreted was 0.04 mg (about 0.18% of the administered dose). RA was not detected in either of the sweat patches probably because of its acidic properties. Measuring MPH in sweat patches can be a viable alternative to urine testing for noninvasive monitoring of use and misuse of the drug. © 2010 by Lippincott Williams & Wilkins.

Pellegrini M.,Istituto Superiore di Sanita | Rotolo M.C.,Istituto Superiore di Sanita | La Grutta S.,National Research Council Italy | Cibella F.,National Research Council Italy | And 5 more authors.
Forensic Science International | Year: 2010

We investigated acute and chronic exposure to environmental tobacco smoke (ETS) in a cohort of young adolescents using urinary cotinine and hair nicotine testing after recent implementation of Italian smoke free legislation. Study subjects were 372 Italian young adolescents, between 10 and 16 years of age from the principal city of Sicily, Palermo. Urine and hair samples were collected between November 2005 and May 2006, when the legislation to ban smoking in all the enclosed places of employment (including bars, restaurants, pubs) was completely enforced. An exhaustive questionnaire including sociodemographic characteristics and active and passive exposure to cigarette smoking was completed. Urinary cotinine was analyzed by radioimmunoassay and hair nicotine by a validated GC/MS method. Based on urinary cotinine results, 2.1% and 89% of the study participants, respectively, showed non-exposure and low acute exposure to ETS, whereas only 1.6% presented very high exposure or a hidden active smoking habit in the recent past. Hair nicotine disclosed non-exposure and low exposure to ETS in 11.8% and 65.6% of the young adolescents, respectively, taking into consideration a larger time-window. High repeated exposure, suggesting active smoking in some cases was observed in 8.6% of the study subjects. Hair nicotine was inversely related to educational level of the adolescents' parents. Overall, due to the implementation of smoke-free legislation and information campaign against smoking, a significant trend toward low exposure to ETS was observed in this study cohort with no association between exposure to ETS and respiratory illnesses. © 2009 Elsevier Ireland Ltd. All rights reserved.

Papaseit E.,Autonomous University of Barcelona | Marchei E.,Istituto Superiore di Sanita | Farre M.,Autonomous University of Barcelona | Garcia-Algar O.,Unitat de Recerca Infancia i Entorn URIE | And 2 more authors.
Drug Testing and Analysis | Year: 2013

Atomoxetine (ATX) is a non-stimulant drug approved for the treatment of children and adolescents with attention deficit/hyperactivity disorder (ADHD). We aimed to study the excretion profile of ATX and its principal metabolites 4-hydroxyatomoxetine (4-OH-ATX) and N-desmethylatomoxetine (desmethyl-ATX) in oral fluid and plasma of ADHD paediatric subjects, after administration of different dosage regimens. Oral fluid and plasma samples were obtained from one child and five adolescents treated with different ATX doses (18-60mg/day). ATX and its metabolites were measured in oral fluid and plasma by liquid chromatography-mass spectrometry (LC-MS). Apparent pharmacokinetic parameters of ATX in oral fluid and plasma were estimated for each subject. All analytes under investigation were detected in plasma samples with concentrations from 0.6 to 1065.7ng/ml for ATX, 0.7 to 17.1ng/ml for 4-OH-ATX and 0.7 to 126.2ng/ml for desmethyl-ATX. Only ATX and 4-OH-ATX were detected in oral fluid samples with concentrations from 0.5 to 36.0ng/ml and 0.5 to 4.7ng/ml, respectively. ATX concentrations in oral fluid were between one and two orders of magnitude lower than those in plasma. 4-OH-ATX was found in oral fluid at a peak concentration approximately one-fourth those in plasma with a mean tmax of 2.3 in plasma and 3.0h in oral fluid. The correlations between ATX and 4-OH-ATX concentrations in the two biological fluids indicate that oral fluid concentrations of this drug and its principal metabolite may be a predictor of plasma concentrations, even if values are too low and variable to be considered an alternative to plasma. © 2012 John Wiley & Sons, Ltd.

Marchei E.,Istituto Superiore di Sanita | Farre M.,University of the Sea | Pardo R.,University of the Sea | Garcia-Algar O.,Unitat de Recerca Infancia i Entorn URIE | And 3 more authors.
Clinical Chemistry | Year: 2010

BACKGROUND: We studied the excretion profile of methylphenidate (MPH) and its metabolite ritalinic acid (RA) in oral fluid and plasma, the oral fluid-toplasma (OF/P) drug ratio, and the variations of oral fluid pH after drug administration. METHODS: We analyzed oral fluid and plasma samples, obtained from 8 healthy volunteers after ingestion of a single dose of 20 mg fast-release or extended-release MPH, for MPH and RA by LC-MS. We estimated the apparent pharmacokinetic parameters of MPH in plasma and oral fluid and calculated the OF/P ratio for each time interval. RESULTS: MPH and RA were detected in oral fluid. Whereas parent drug concentrations in oral fluid were an order of magnitude higher than those in plasma, the opposite was observed for RA. Oral fluid concentrations of MPH ranged between 0.5 and 466.7 μg/L and peaked at 0.5 h after administration of the fast-release formulation; they ranged between 0.7 and 89.5 μg/L and peaked at 2 h after administration of the extendedrelease formulation. Both formulations presented bimodal time-course curves for the OF/P ratio, ranging between 1.8 and 242.1 for the fast-release formulation and between 2.6 and 27.0 for extended-release. Oral fluid pH did not appear to be modified by the administration of the drug, and its influence on OF/P ratio did not affect the correlation of MPH between the 2 body fluids. CONCLUSIONS: The results obtained support the measurement of MPH in oral fluid as an alternative to plasma if the extended-release formulation is used. © 2010 American Association for Clinical Chemistry.

Manich A.,Unitat de Recerca Infancia i Entorn URIE | Velasco M.,Unitat de Recerca Infancia i Entorn URIE | Joya X.,Unitat de Recerca Infancia i Entorn URIE | Garcia-Lara N.R.,Servicio de Neonatologia | And 3 more authors.
Anales de Pediatria | Year: 2012

Introduction: Ethanol consumption by pregnant women can produce severe effects in the foetus and the newborn, mainly in neurological and weight-height development, and are included in the term FASD (Fetal Alcohol Spectrum Disorder). Questionnaires are the most used screening method to detect prenatal exposure, but a previous population study questioned its reliability. The objective of this study was to compare alcohol prenatal exposure detection by questionnaire compared with biomarkers in meconium. Methodology: Sixty two meconium samples from mothers who denied alcohol consumption during pregnancy by questionnaire were analysed. The objective analysis was made by determination of FAEEs (fatty acid ethyl esters) as exposure biomarkers in meconium as biological matrix. Results: In the meconium from 10 of 62 newborns from non-alcohol consuming mothers by questionnaire (16.12%) FAEE values were positive (≥ 2 nmol/g). Discussion: Questionnaires as a screening method during pregnancy are not a reliable tool. It is necessary to identify prenatal exposure to alcohol as soon as possible by biomarkers analysis in biological matrices from the newborn or the mother. The early detection will allow these patients to benefit from follow up and treatment to reach the best possible neurological development. © 2012 Asociación Españolade Pediatría. Published by Elsevier España, S.L. All rights reserved.

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