Dataset Information

Pharmacokinetics of Oral and Inhaled Terbutaline after Exercise in Trained Men.

ABSTRACT: AIM:The aim of the study was to investigate pharmacokinetics of terbutaline after oral and inhaled administration in healthy trained male subjects in relation to doping control. METHODS:Twelve healthy well-trained young men (27 ±2 years; mean ± SE) underwent two pharmacokinetic trials that compared 10 mg oral terbutaline with 4 mg inhaled dry powder terbutaline. During each trial, subjects performed 90 min of bike ergometer exercise at 65% of maximal oxygen consumption. Blood (0-4 h) and urine (0-24 h) samples were collected before and after administration of terbutaline. Samples were analyzed for concentrations of terbutaline by high performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). RESULTS:Pharmacokinetics differed between the two routes of administration. Serum Cmax and area under the serum concentration-time curve (AUC) were lower after oral administration compared to inhalation (Cmax: 4.2 ± 0.3 vs. 8.5 ± 0.7 ng/ml, P ? 0.001; AUC: 422 ± 22 vs. 1308 ± 119 ng/ml × min). Urine concentrations (sum of the free drug and the glucuronide) were lower after oral administration compared to inhalation 2 h (1100 ± 204 vs. 61 ± 10 ng/ml, P ? 0.05) and 4 h (734 ± 110 vs. 340 ± 48 ng/ml, P ? 0.001) following administration, whereas concentrations were higher for oral administration than inhalation 12 h following administration (190 ± 41 vs. 399 ± 108 ng/ml, P ? 0.05). Urine excretion rate was lower after oral administration than inhalation the first 2 h following administration (P ? 0.001). Systemic bioavailability ratio between the two routes of administration was 3.8:1 (inhaled: oral; P ? 0.001). CONCLUSION:Given the higher systemic bioavailability of inhaled terbutaline compared to oral, our results indicate that it is difficult to differentiate allowed inhaled use of terbutaline from prohibited oral ingestion based on urine concentrations in doping control analysis. However given the potential performance enhancing effect of high dose terbutaline, it is essential to establish a limit on the WADA doping list.

SUBMITTER: Dyreborg A

PROVIDER: S-EPMC4901060 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Pharmacokinetics of Oral and Inhaled Terbutaline after Exercise in Trained Men.

Dyreborg Anders A Krogh Nanna N Backer Vibeke V Rzeppa Sebastian S Hemmersbach Peter P Hostrup Morten M

Frontiers in pharmacology 20160610

<h4>Aim</h4>The aim of the study was to investigate pharmacokinetics of terbutaline after oral and inhaled administration in healthy trained male subjects in relation to doping control.<h4>Methods</h4>Twelve healthy well-trained young men (27 ±2 years; mean ± SE) underwent two pharmacokinetic trials that compared 10 mg oral terbutaline with 4 mg inhaled dry powder terbutaline. During each trial, subjects performed 90 min of bike ergometer exercise at 65% of maximal oxygen consumption. Blood (0-4 ...[more]

PMID: 27375484

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Project description:The purpose of this investigation was to compare changes in circulating lymphocyte subset cell counts between high-intensity interval exercise (HIIE), sprint interval exercise (SIE), and moderate-intensity continuous exercise (MICE). Recreationally active men (n = 11; age: 23 ± 4 yr; height: 179.9 ± 4.5 cm; body mass: 79.8 ± 8.7 kg; body fat %:12.6 ± 3.8%; V̇O2max: 46.6 ± 3.9 ml⋅kg-1⋅min-1) completed a maximal graded exercise test to determine maximal oxygen uptake (V̇O2max) and three duration-matched cycling trials (HIIE, SIE, and MICE) in a randomized, counterbalanced fashion. HIIE consisted of fifteen 90-s bouts at 85% V̇O2max interspersed with 90-s active recovery periods. SIE consisted of fifteen 20-s bouts at 130% maximal power and 160-s active recovery periods. MICE was a continuous bout at 65% V̇O2max. Total exercise duration was 53 min in all three trials, including warm-up and cool-down. Blood was collected before, immediately post, 30 min, 2 h, 6 h, and 24 h post-exercise. Changes in lymphocyte subset counts, and surface expression of various markers were analyzed via flow cytometry. Changes were assessed using mixed model regression analysis with an autoregressive first order repeated measures correction. Significant decreases were observed in absolute counts of CD56dim NK cells, CD19+ B cells, CD4+ T cells, and CD8+ T cells 30 min and 24-h post-exercise in all three trials. Despite resulting in greater total work and oxygen consumption, MICE elicited similar changes in lymphocyte subset counts and receptor expression compared to both SIE and HIIE. Similarly, while the two interval trials resulted in differing oxygen consumption and total work, no differences in the lymphocyte response were observed. Though both forms of exercise resulted in declines in circulating lymphocyte cell counts, neither exercise type provides an immune-related advantage when matched for duration.

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Dataset Information

Pharmacokinetics of Oral and Inhaled Terbutaline after Exercise in Trained Men.

Publications

Pharmacokinetics of Oral and Inhaled Terbutaline after Exercise in Trained Men.

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