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Elers J.,Respiratory Research Unit | Pedersen L.,Respiratory and Allergy Research Unit | Henninge J.,University of Oslo | Hemmersbach P.,University of Oslo | And 2 more authors.
International Journal of Sports Medicine | Year: 2011

We examined blood and urine concentrations of repetitive doses of inhaled salbutamol in relation to the existing cut-off value used in routine doping control. We compared the concentrations in asthmatics with regular use of beta2-agonists prior to study and healthy controls with no previous use of beta2-agonists. We enrolled 10 asthmatics and 10 controls in an open-label study in which subjects inhaled repetitive doses of 400microgram salbutamol every second hour (total 1600microgram), which is the permitted daily dose by the World Anti-Doping Agency (WADA). Blood samples were collected at baseline, 30min, 1, 2, 3, 4, and 6h after the first inhalations. Urine samples were collected at baseline, 04h, 48h, and 812h after the first inhalations. Median urine concentrations peaked in the period 48h after the first inhalations in the asthmatics and between 812h in controls and the median ranged from 268 to 611ng×mL1. No samples exceeded the WADA threshold value of 1000ng×mL1 when corrected for the urine specific gravity. When not corrected one sample exceeded the cut-off value with urine concentration of 1082ng×mL1. In conclusion we found no differences in blood and urine concentrations between asthmatic and healthy subjects. We found high variability in urine concentrations between subjects in both groups. The variability between subjects was still present after the samples were corrected for urine specific gravity. © Georg Thieme Verlag KG Stuttgart - New York.

Mareck U.,German Sport University Cologne | Guddat S.,German Sport University Cologne | Schwenke A.,German Sport University Cologne | Beuck S.,German Sport University Cologne | And 6 more authors.
Drug Testing and Analysis | Year: 2011

The determination of salbutamol and its glucuronide in human urine following the inhalative and oral administration of therapeutic doses of salbutamol preparations was performed by means of direct urine injection utilizing liquid chromatography-tandem mass spectrometry (LC-MS/MS) and employing d 3-salbutamol and d 3-salbutamol glucuronide as internal standards. Unconjugated salbutamol was detected in all administration study urine samples. Salbutamol concentrations following inhalation were commonly (99%) below 1000ng/ml whereas values after oral administration frequently (48%) exceeded this threshold. While salbutamol glucuronide was not detected in urine samples collected after inhalation of the drug, 26 out of 82 specimens obtained after oral application contained salbutamol glucuronide with a peak value of 63ng/ml. The percentage of salbutamol glucuronide compared to unconjugated salbutamol was less than 3%. Authentic doping control urine samples indicating screening results for salbutamol less than 1000ng/ml, showed salbutamol glucuronide concentrations between 2 and 6ng/ml, whereas adverse analytical findings resulting from salbutamol levels higher than 1000ng/ml, had salbutamol glucuronide values between 8 and 15ng/ml. The approach enabled the rapid determination of salbutamol and its glucuronic acid conjugate in human urine and represents an alternative to existing procedures since time-consuming hydrolysis or derivatization steps were omitted. Moreover, the excretion of salbutamol glucuronide in human urine following the administration of salbutamol was proven. © 2011 John Wiley & Sons, Ltd.

Meteran H.,Respiratory and Allergy Research Unit | Backer V.,Respiratory and Allergy Research Unit | Kyvik K.O.,University of Southern Denmark | Skytthe A.,University of Southern Denmark | Thomsen S.F.,Respiratory and Allergy Research Unit
Respiratory Medicine | Year: 2014

Background Smoking is a major risk factor for lung diseases and lower respiratory symptoms, but since not all smokers develop chronic bronchitis and since chronic bronchitis is also diagnosed in never-smokers, it has been suggested that some individuals are more susceptible to develop chronic bronchitis due to genetics. Objective To study the relative influence of genetic and environmental factors on the variation in the susceptibility to chronic bronchitis. Methods In a population-based questionnaire study of 13,649 twins, 50-71 years of age, from the Danish Twin Registry, we calculated sex-specific concordance rates and heritability of chronic bronchitis. The response rate was 75%. Results The prevalence of chronic bronchitis was 9.3% among men and 8.5% among women. The concordance rate for chronic bronchitis was higher in monozygotic twins than in dizygotic twins among women; 0.30 vs. 0.17, but not among men; 0.15 vs. 0.18. The heritability of chronic bronchitis adjusted for smoking and age was 55% (36-71%) in women, whereas the susceptibility to chronic bronchitis in men for 25% (8-41%) was ascribable to familial environment but not to genetic factors. Conclusions Chronic bronchitis shows a moderate familial aggregation, particularly in women. Increased susceptibility to respiratory disease among female smokers relative to male smokers may have a genetic origin. © 2014 Elsevier Ltd.

Elers J.,Respiratory and Allergy Research Unit | Pedersen L.,Respiratory and Allergy Research Unit | Henninge J.,University of Oslo | Lund T.K.,Respiratory and Allergy Research Unit | And 3 more authors.
Medicine and Science in Sports and Exercise | Year: 2010

Purpose: Data on blood and urinary concentrations of salbutamol after inhalation and oral administration in healthy subjects are scarce. Accordingly, we examined the pharmacokinetics of inhaled and oral salbutamol in asthmatic subjects. Methods: We enrolled 10 men aged 18-45 yr in an open-label study in which 0.8 mg of inhaled or 8 mg of systemic salbutamol was administered in a crossover design. All subjects had doctor-diagnosed asthma, used β2 agonist when needed, and abstained from any medicine, β2 agonist inclusive, for 14 d before visit. Urine was collected from all subjects (0-4, 4-8, and 8-12 h), and blood samples were taken at 0, 0.5, 1, 2, 3, 4, and 6 h after salbutamol administration. Results: Maximum urine concentration was reached during the first 4 h after administration of both inhaled and oral salbutamol. We found differences in median urinary concentrations (Cmax) of 260.9 and 2422.2 ng•mL, respectively (P < 0.005). Urinary concentrations show high individual variability irrespective of the route of administration. Blood analyses showed a systemic exposure of salbutamol after both inhaled and oral salbutamol with peak concentration after inhalation before the oral intake (P < 0.05). A difference in median Cmax after inhalation and oral treatment was found: 1.75 and 18.77 ng•mL, respectively (P < 0.05). Conclusions: Median urinary concentrations after oral administration of 8 mg of salbutamol were significantly higher than those after inhalation of 0.8 mg of salbutamol. Copyright © 2010 by the American College of Sports Medicine.

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