Pharmacokinetics of oral and inhaled terbutaline after exercise in trained men

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 C(max) and area under the serum concentration-time curve (AUC) were lower after oral administration compared to inhalation (C(max): 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

Impact of adrenaline and metabolic stress on exercise-induced intracellular signaling and PGC-1α mRNA response in human skeletal muscle

This study tested the hypothesis that elevated plasma adrenaline or metabolic stress enhances exercise‐induced PGC‐1α mRNA and intracellular signaling in human muscle. Trained (VO (2)‐max: 53.8 ± 1.8 mL min(−1) kg(−1)) male subjects completed four different exercise protocols (work load of the legs was matched): C – cycling at 171 ± 6 W for 60 min (control); A – cycling at 171 ± 6 W for 60 min, with addition of intermittent arm exercise (98 ± 4 W). DS – cycling at 171 ± 6 W interspersed by 30 sec sprints (513 ± 19 W) every 10 min (distributed sprints); and CS – cycling at 171 ± 6 W for 40 min followed by 20 min of six 30 sec sprints (clustered sprints). Sprints were followed by 3:24 min:sec at 111 ± 4 W. A biopsy was obtained from m. vastus lateralis at rest and immediately, and 2 and 5 h after exercise. Muscle PGC‐1α mRNA content was elevated (P < 0.05) three‐ to sixfold 2 h after exercise relative to rest in C, A, and DS, with no differences between protocols. AMPK and p38 phosphorylation was higher (P < 0.05) immediately after exercise than at rest in all protocols, and 1.3‐ to 2‐fold higher (P < 0.05) in CS than in the other protocols. CREB phosphorylation was higher (P < 0.05) 2 and 5 h after exercise than at rest in all protocols, and higher (P < 0.05) in DS than CS 2 h after exercise. This suggests that neither plasma adrenaline nor muscle metabolic stress determines the magnitude of PGC‐1α mRNA response in human muscle. Furthermore, higher exercise‐induced changes in AMPK, p38, and CREB phosphorylation are not associated with differences in the PGC‐1α mRNA response

Nonpharmacologic Strategies to Manage Exercise-Induced Bronchoconstriction

Pharmacological management of exercise induced bronchoconstriction (EIB) is the mainstay of preventative therapy. However, there are some non-pharmacological interventions that may assist the management of EIB. In this review we will discuss these non-pharmacological interventions and how they may be applied to patients and athletes with EIB