Urine and Serum Concentrations of Inhaled and Oral Terbutaline

Abstract

We examined urine and serum concentrations after therapeutic use of single and repetitive doses of inhaled and supratherapeutic oral use of terbutaline. We compared the concentrations in 10 asthmatics and 10 healthy subjects in an open-label, cross-over study with 2 mg inhaled and 10 mg oral terbutaline on 2 study days. Further, 10 healthy subjects were administrated 1 mg inhaled terbutaline in 4 repetive doses with total 4 mg. Blood samples were collected at baseline and during 6 h after the first inhalations. Urine samples were collected at baseline and during 12 h after the first inhalations. Median (IQR) urine concentrations peaked in the period 0-4 h after inhalation with Cmax 472 (324) ng/mL in asthmatics and 661 (517) ng/mL in healthy subjects, and 4-8 h after oral use with Cmax 666 (877) ng/mL in asthmatic and 402 (663) ng/mL in healthy subjects. In conclusion we found no significant differences in urine and serum concentrations between asthmatic and healthy subjects. We compared urine and serum concentrations after therapeutic inhaled doses and supratherapeutic oral doses and observed significant statistical differences in both groups but found it impossible to distinguish between therapeutic and prohibited use based on doping tests with urine and blood samples.

High-dose inhaled terbutaline increases muscle strength and enhances maximal sprint performance in trained men

“…Mean ± SEM administration. Noteworthy, the systemic concentrations observed were 4 times higher than that observed by Elers et al (2012a) after oral administration of 10 mg terbutaline with reported peak systemic concentrations of only 6.2 ± 4.8 ng ml −1 (median ± interquartile range). Likewise, we observed several indications of systemic effects of inhaled terbutaline, including elevated V O 2 at rest and during submaximal exercise at 80 % of V O 2max , along with lowered systemic concentrations of K + and elevated concentrations of glucose and lactate.…”

“…Active substance (Terbutaline, Bricanyl Turbohaler 0.5 mg) was delivered by the Pharmacy of RegionH, Copenhagen, Denmark. Inhaled terbutaline has been shown to be quickly absorbed, reaching peak systemic concentrations (C max ) 30 min (T max ) following administration (Elers et al 2012a). The onset of action of inhaled terbutaline is within a few minutes with a duration of action of up to 6 h (datasheet, Bricanyl ® Turbohaler, AstraZeneca).…”

“…Samples were shipped (World Courier) on dry ice from Copenhagen. Concentrations of terbutaline in serum were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) as described by Elers et al (2012a). A person with no involvement in other parts of the experimental procedures administered the study drugs.…”

“…Indeed, Elers et al (2012a) observed that inhalation of 2 mg terbutaline gave similar systemic concentrations as oral administration of 10 mg terbutaline. Moreover, if calculating the area under the curve (AUC) of the systemic concentrations of terbutaline in the study by Elers et al (2012a), results indicate a higher systemic bioavailability following inhalation, with AUC being 25.1 ± 5.6 ng ml −1 h after inhalation of 2 mg and 24.6 ± 7.1 ng ml −1 h after oral administration of 10 mg. Schmekel et al (1992) also observed that the peak systemic concentrations of terbutaline achieved after inhalation of 1 mg terbutaline equivocated with that observed by Bengtsson and Fagerstrom (1982) after administration of 5 mg oral terbutaline (Schmekel et al 1992;Bengtsson and Fagerstrom 1982). It is therefore possible that supratherapeutic high-dose inhalation of beta 2 -agonists imposes a similar systemic response as that observed from oral administration (Elers et al 2012a, c), hence being performance enhancing.…”

Effect of inhaled terbutaline on substrate utilization and 300-kcal time trial performance

“…Briefly, blood samples were collected in vacutainers with clot activator and spun at 3,000 rpm for 15 min, after which serum samples were collected and stored at Ϫ80°C. Serum TER was analyzed by liquid chromatography-tandem mass spectrometry as previously described (11) and performed by the World Anti-Doping Agency-accredited Norwegian Doping Control Laboratory at Oslo University Hospital, in Oslo, Norway.…”