GRAZ – As the delivery of drugs to the body through the lungs becomes a treatment option for diseases such as diabetes mellitus, possible interactions with other inhalative medications must be taken into consideration. A new study has found that some asthma patients are more susceptible to inhaled insulin if it is applied after the use of a bronchodilator such as terbutaline.

Professor Thomas R Pieber of the Department of Internal Medicine at the University of Graz, Austria, and colleagues conducted an open-label study in 41 nondiabetic asthma patients treated with inhaled steroids.

Pulmonary function tests [FEV1, forced vital capacity (FVC) and FEV1/FVC] were performed according to criteria in accordance with the European Respiratory Society standards.

They differentiated between patients with reversible bronchoconstriction (n = 25) and those without (n = 16).

Patients received a dose of 0.10 Units per kilogram bodyweight inhaled human insulin on each of the two dosing days, with or without prior administration of the bronchodilator terbutaline.

The study, published in the British Journal of Clinical Pharmacology, found that prior administration of terbutaline led to a 44% increase in absorption of insulin over 6 h for the group positive for reversible bronchoconstriction (compared with no prior administration of bronchodilator), whereas no effect was seen for the group without reversible bronchoconstriction or the group as a whole. The maximum insulin concentration (Cmax) increased by 34% for the reversible group and by 17% for the whole group, whereas no significant effect of prior terbutaline administration was seen for the non-reversible group.

“In patients with asthma and reversible bronchoconstriction, the administration of a bronchodilator prior to administration of inhaled insulin led to increased absorption of insulin, whereas no effect on insulin absorption in subjects without significant reversibility could be demonstrated,” write the researchers.

Terbutaline and other beta-2-agonists increase blood glucose via adrenergic stimulation, and have even been tested in the prevention of hypoglycaemia in diabetic patients. Due to this glucose-increasing effect of terbutaline, the insulin-induced drop in plasma glucose was not as pronounced, compared with the pharmacokinetic response, on the days with terbutaline administration.

In summary, the study has shown that in people with asthma and reversible bronchoconstriction, the administration of a bronchodilator prior to administration of inhaled insulin leads to increased absorption of insulin, whereas no effect in subjects without significant reversibility could be found.

Clinical implication

Two factors need to be taken into account when treating patients who suffer from both asthma and diabetes:

Firstly, that the bioavailability of inhaled insulin is reduced by the presence of bronchoconstriction in asthmatic subjects. This phenomenon of reduced bioavailability may depend not only on bronchoconstriction but also on inflammatory changes in the airway mucosa, the authors explain.

Secondly, physicians should be aware of the potential glucose-increasing effect of terbutaline, and adjust diabetes treatment accordingly.

Reference:
Petersen AH, et al. Br J Clin Pharmacol. 2010 Mar;69(3):271-8.