title: Pharmacokinetics of methylphenidate in oral fluid and sweat of a pediatric subject.
abstract: Methylphenidate (MPH) is a stimulant medication widely used for treating attention-deficit hyperactivity disorder (ADHD) in children and adolescents. Therapeutic monitoring for this drug is essentially lacking and alternative biological matrices, such as oral fluid and sweat, should be investigated for noninvasive assessment of short- and long-term history of drug use. We report the excretion profile of MHP and its metabolite ritalinic acid (RA) in oral fluid and sweat from a 12-year-old boy treated with the extended release drug formulation. Concentrations of MPH and RA in oral fluid, sweat and plasma were measured by liquid chromatography-mass spectrometry. Oral fluid-to-plasma ratio at each time interval was calculated at the start of the treatment and correlated with salivary pH. Excretion of MPH in sweat patches, collected up to 24h with PharmChek patches was also investigated. MPH and RA were both detected in oral fluid with a pharmacokinetic profile similar to that in plasma. Oral fluid peak concentrations of MPH ranged between 13.5 and 30.9 ng/mL at 3.0 h after drug intake. Oral fluid-to-plasma MPH ratio between 13.1 and 3.2 demonstrated an accumulation of the drug in oral fluid. Conversely, RA was found in oral fluid at peak concentration (23.4-62.9 ng/mL) equivalent to one-tenth of those found in plasma. Concentration profiles of MPH and RA in oral fluid were quite constant during the four weeks of drug administration. In sweat, MPH was detected for the first time at 5h after drug administration (range: 9.3-11.2 ng/patch) up to 24h (range: 29.8-38.7 ng/patch). RA was not detected in the sweat patches during the 24h time of collection. The results suggest that measurement of MPH in oral fluid can be used as a potential alternative to drug monitoring in plasma. Moreover, MPH measurement in sweat patches can be used for noninvasive monitoring of MPH consumption and misuse in situations where detection of recent abuse is of interest.
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanitá, Rome, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Marchei
authors.forename: M
authors.initials: M
authors.lastname: Farrè
authors.forename: M
authors.initials: M
authors.lastname: Pellegrini
authors.forename: O
authors.initials: O
authors.lastname: García-Algar
authors.forename: O
authors.initials: O
authors.lastname: Vall
authors.forename: R
authors.initials: R
authors.lastname: Pacifici
authors.forename: S
authors.initials: S
authors.lastname: Pichini
mesh_terms: D000697:Central Nervous System Stimulants / Q000032:analysis / Q000493:pharmacokinetics*; D002648:Child; D003692:Delayed-Action Preparations; D016903:Drug Monitoring / Q000379:methods; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000031:analogs & derivatives / Q000032:analysis / Q000493:pharmacokinetics*; D012463:Saliva / Q000737:chemistry*; D013542:Sweat / Q000737:chemistry*
chemical_list: D000697:Central Nervous System Stimulants; D003692:Delayed-Action Preparations; D008774:Methylphenidate; C009189:ritalinic acid