Comparative pharmacokinetics of unlabeled and deuterium-labeled terbutaline: demonstration of a small isotope effect.

An equimolar mixture of terbutaline and [2H6]terbutaline was given as an oral solution to six healthy volunteers (three men and three women). Frequent blood samples were collected during a 24-h period and the plasma concentrations of unlabeled and deuterium-labeled terbutaline were measured by GC-MS. The overall geometric mean plasma concentration ratio of terbutaline to [2H6]terbutaline (isotope ratio) was 1.04 and differed significantly from unity. The difference can be explained by a difference in lipophilicity between the analogues, affecting their absorption. No trend in isotope ratio over the experimental time was observed. For unknown reasons, the isotope ratio was higher for women (1.07) than for men (1.00). Deuterium-labeled terbutaline can be used, intravenously or orally, as an absolute reference in bioavailability studies on terbutaline. If deuterium-labeled terbutaline is given orally in a single-day relative bioavailability study, a correlation should be made for the observed isotope effect.