Terbutaline Accumulates in Blood and Urine after Daily Therapeutic Inhalation

Purpose: This study investigated pharmacokinetics of terbutaline after single and seven consecutive days of inhalation in exercising trained men. Methods: Twelve healthy trained men underwent two pharmacokinetic trials comparing single dose (2 mg) and seven consecutive days (2 mg·d−1) of inhaled terbutaline. After inhalation of terbutaline at each trial, subjects performed 90 min of bike ergometer exercise at 55%–65% of maximal oxygen consumption after which they stayed inactive. Blood and urine samples were collected before and after inhalation of terbutaline. Samples were analyzed by high-performance liquid chromatography–tandem mass spectrometry. Results: Maximum serum concentration of terbutaline (Cmax) (6.4 ± 1.2 vs 4.9 ± 1.2 ng·mL−1, P = 0.01) (mean ± 95% confidence interval) and area under serum concentration–time curve from 0 to 4 h after inhalation (AUC0–4) (16 ± 3 vs 13 ± 2 ng·mL−1·h−1, P ≤ 0.005) were higher after 7 d of inhalation compared with the first day. Seven days of terbutaline inhalation resulted in accumulation of terbutaline in urine, in which total urine excretion of terbutaline was higher after 7 d of inhalation compared with the first day (274 ± 43 vs 194 ± 33 μg, P ≤ 0.001). These differences were partly attributed to systemic accumulation of terbutaline after consecutive days of inhalation, in that baseline serum and urine samples revealed incomplete elimination of terbutaline. Conclusion: Terbutaline accumulates in serum and urine after consecutive days of inhalation. For doping control purposes, these observations are of relevance if a urine threshold and decision limit is to be introduced for terbutaline on the World Anti-Doping Agency's list of prohibited substances because asthmatic athletes may use their bronchorelievers for consecutive days.

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