In vitro and in vivo pharmacologic studies have demonstrated that terbutaline exerts a preferential effect on beta 2-adrenergic receptors. While it is recognized that beta2-adrenergic receptors are the predominant receptors in bronchial smooth muscle, data indicate that there is a population of beta2-receptors in the human heart, existing in a concentration between 10% to 50%. The precise function of these receptors has not been established [see  WARNINGS]. In controlled clinical studies in patients given terbutaline sulfate orally, proportionally greater changes occurred in pulmonary function parameters than in heart rate or blood pressure. While this suggests a relative preference for the beta 2-receptors in man, the usual cardiovascular effects commonly associated with other sympathomimetic agents were also observed with terbutaline sulfate. 

The pharmacologic effects of beta-adrenergic agonists, including terbutaline, are at least in part attributable to stimulation through beta-adrenergic receptors of intracellular adenyl cyclase, the enzyme which catalyzes the conversion of adenosine triphosphate (ATP) to cyclic 3’, 5’-adenosine monophosphate (cAMP). Increased cAMP levels are associated with relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells.

Controlled clinical studies have shown that terbutaline sulfate relieves bronchospasm in chronic obstructive pulmonary disease by significantly increasing pulmonary function (e.g., an increase of 15% or more in FEV 1 and in FEF 25%-75%). After administration of terbutaline sulfate tablets, a measurable change in flow rate usually occurs within 30 minutes, and a clinically significant improvement in pulmonary function occurs within 60 to 120 minutes. The maximum effect usually occurs within 120 to 180 minutes. Terbutaline sulfate also produces a clinically significant decrease in airway and pulmonary resistance, which persists for 4 hours or longer. Significant bronchodilator action (as measured by airway resistance, FEF 25%-75% or PEFR) has also been demonstrated for up to 8 hours in some studies. 

In studies comparing the effectiveness of terbutaline sulfate with that of ephedrine for up to 3 months, both drugs maintained a significant improvement in pulmonary function throughout this period of treatment.

Preclinical

Studies in laboratory animals (minipigs, rodents, and dogs) have demonstrated the occurrence of cardiac arrhythmias and sudden death (with histologic evidence of myocardial necrosis) when beta-agonists and methylxanthines were administered concurrently. The clinical significance of these findings is unknown.

Pharmacokinetics

Oral administration of 5-mg terbutaline sulfate tablets or 5 mg terbutaline sulfate in solution in 17 healthy, adult, male subjects, resulted in mean (SD) peak plasma terbutaline concentration of 8.3 (3.9) and 8.6 (3.6) ng/mL, which were observed at median (range) times of 2 (1 to 3) and 1.5 (0.5 to 3.0) hours after dosing. The mean (SD) AUC (0-48) values were 54.6 (26.8) and 53.1 (23.5) hr•ng/mL, and corresponded to a bioavailability of 103% for the tablet relative to the solution. 

After oral administration of terbutaline, 51 to 62 mcg/kg of body weight, to 3 healthy male subjects, peak serum levels of 3.1 to 6.2 ng/mL were observed 1 to 3 hours later. In the same study, after 3 days only 30% to 50% of the dose was recovered from urine and the remainder from the feces, which may indicate poor absorption.

After an oral dose to asthmatic patients, the elimination half-life of terbutaline was approximately 3.4 hours.

In comparison to oral dosing, subcutaneous administration of 0.5 mg of terbutaline sulfate to 17 healthy, adult, male subjects resulted in a mean (SD) peak plasma terbutaline concentration of 9.6 (3.6) ng/mL, which was observed at a median (range) time of 0.5 (0.08 to 1.0) hours after dosing. The mean (SD) AUC (0-48) and total body clearance values were 29.4 (14.2) hr•ng/mL, and 311 (112) mL/min, respectively. The terminal half-life was determined in 9 of the 17 subjects and had a mean (SD) of 5.7 (2.0) hours. 

About 90% of the drug was excreted in the urine at 96 hours after subcutaneous administration, with about 60% of this being unchanged drug. The sulfate conjugate is a major metabolite of terbutaline, and urinary excretion is the primary route of elimination.

There are no reports of any clinical pharmacokinetic studies investigating dose proportionality, effect of food, or special population studies with terbutaline.