TY - JOUR

T1 - Pharmacokinetics of nebulized and oral procaterol in asthmatic and non-asthmatic subjects in relation to doping analysis

AU - Krogh, Nanna

AU - Backer, Vibeke

AU - Rzeppa, Sebastian

AU - Hemmersbach, Peter

AU - Hostrup, Morten

N1 - CURIS 2016 NEXS 097

PY - 2016

Y1 - 2016

N2 - 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 ± 1 2 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 ofprocaterol 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 proh ib ited use of oral procaterol.

AB - 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 ± 1 2 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 ofprocaterol 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 proh ib ited use of oral procaterol.

KW - Faculty of Science

KW - Doping

KW - Pharmacology

KW - Beta2-adrenoceptor agonists

KW - WADA

KW - Urine specific gravity

U2 - 10.1002/dta.1935

DO - 10.1002/dta.1935

M3 - Journal article

C2 - 26990656

VL - 8

SP - 1056

EP - 1064

JO - Drug Testing and Analysis

JF - Drug Testing and Analysis

SN - 1942-7603

IS - 10

ER -