title: First report on the pharmacokinetics of tramadol and O-desmethyltramadol in exhaled breath compared to plasma and oral fluid after a single oral dose.
abstract: Exhaled breath (EB) is a promising matrix for bioanalysis of non-volatiles and has been routinely implemented for drugs of abuse analysis. Nothing is known regarding the pharmacokinetics of therapeutics and their metabolites in EB. Therefore, we used tramadol as a model drug. Twelve volunteers received a single oral dose of tramadol and repeated sampling of EB, plasma, and oral fluid (OF) was done for 48 h using a particle filter device for EB and the Quantisal-device for OF. Samples were analyzed with LC-MS/MS and the pharmacokinetic correlations between matrices were investigated. The initial tramadol half-life in EB was shorter than in plasma but it reappeared in EB after 8-24 h. The ratio of O-desmethyltramadol to tramadol was considerably lower in EB and OF compared to plasma. This pilot study compared for the first time the pharmacokinetics of a therapeutic drug and active metabolite in different biomatrices including EB and demonstrated its potential for bioanalysis.
authors.affiliation: Karolinska Institutet, Department of Laboratory Medicine, Division of Clinical Pharmacology, Stockholm, Sweden. Electronic address: markusr.meyer@gmx.de.
authors.forename: Markus R
authors.initials: MR
authors.lastname: Meyer
authors.affiliation: Karolinska Institutet, Department of Laboratory Medicine, Division of Clinical Pharmacology, Stockholm, Sweden; Karolinska University Laboratory, Department of Clinical Pharmacology, Stockholm, Sweden.
authors.forename: Staffan
authors.initials: S
authors.lastname: Rosenborg
authors.affiliation: Karolinska University Laboratory, Department of Clinical Pharmacology, Stockholm, Sweden.
authors.forename: Marta
authors.initials: M
authors.lastname: Stenberg
authors.affiliation: Karolinska Institutet, Department of Laboratory Medicine, Division of Clinical Pharmacology, Stockholm, Sweden; Karolinska University Laboratory, Department of Clinical Pharmacology, Stockholm, Sweden.
authors.forename: Olof
authors.initials: O
authors.lastname: Beck
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001944:Breath Tests; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D012463:Saliva / Q000378:metabolism*; D014147:Tramadol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000701:Analgesics, Opioid; C080580:O-demethyltramadol; D014147:Tramadol
keywords: Blood plasma; Exhaled breath; LC–MS/MS; Oral fluid; Pharmacokinetics; Tramadol