title: Pharmacokinetics of nebulized and oral procaterol in asthmatic and non-asthmatic subjects in relation to doping analysis.
abstract: The purpose of the present study was to investigate pharmacokinetics of procaterol in asthmatics and non-asthmatics after nebulized and oral administration in relation to doping. Ten asthmatic and ten non-asthmatic subjects underwent two pharmacokinetic trials. At first trial, 4 µg procaterol was administered as nebulization. At second trial, 100 µg procaterol was administered orally. Serum and urine samples were collected before and after administration of procaterol. Samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Serum and urine concentrations of procaterol were markedly higher after oral administration compared to nebulized administration. After oral administration, serum procaterol concentration-time area under the curve (AUC) was higher (P ≤ 0.05) for asthmatics than non-asthmatics. Likewise, urine concentrations were higher (P ≤ 0.01) for asthmatics than non-asthmatics 4 (47 ± 12 vs. 28 ± 9 ng/mL) and 8 h (39 ± 9 vs. 15 ± 5 ng/mL) after oral administration. Detection of serum procaterol was difficult after nebulized administration with 38 samples (27%) below limit of quantification (LOQ) and only trends were observed. No differences were observed between asthmatics and non-asthmatics in the urine concentrations of procaterol after nebulized administration. In summary, our data showed that asthmatics had higher urine concentrations of procaterol than non-asthmatics after oral administration of 100 µg, whereas no difference was observed between the groups after nebulized administration. For doping control purposes, our observations indicate that it is possible to differentiate therapeutic nebulized administration of procaterol from prohibited use of oral procaterol. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Respiratory Research Unit, Bispebjerg University Hospital, Copenhagen, Denmark.
authors.forename: Nanna
authors.initials: N
authors.lastname: Krogh
authors.affiliation: Respiratory Research Unit, Bispebjerg University Hospital, Copenhagen, Denmark.|IOC Sports Medicine, Copenhagen, Denmark.
authors.forename: Vibeke
authors.initials: V
authors.lastname: Backer
authors.affiliation: Norwegian Doping Control Laboratory, Oslo University Hospital, Oslo, Norway.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Rzeppa
authors.affiliation: Norwegian Doping Control Laboratory, Oslo University Hospital, Oslo, Norway.
authors.forename: Peter
authors.initials: P
authors.lastname: Hemmersbach
authors.affiliation: Respiratory Research Unit, Bispebjerg University Hospital, Copenhagen, Denmark. mortenhostrup@gmail.com.|IOC Sports Medicine, Copenhagen, Denmark. mortenhostrup@gmail.com.|Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark. mortenhostrup@gmail.com.
authors.forename: Morten
authors.initials: M
authors.lastname: Hostrup
mesh_terms: D000280:Administration, Inhalation; D000284:Administration, Oral; D058666:Adrenergic beta-2 Receptor Agonists / Q000737:chemistry / Q000652:urine*; D001249:Asthma / Q000188:drug therapy*; D002853:Chromatography, Liquid / Q000379:methods*; D004300:Doping in Sports; D006801:Humans; D017265:Procaterol / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D017265:Procaterol
keywords: WADA; beta2-adrenoceptor agonists; doping; pharmacology; urine specific gravity