Local Versus Total Systemic Bioavailability as a Means to Compare Different Inhaled Formulations of the Same Substance

ABSTRACT

For inhaled formulations of a drug substance, the balance between desired local activity and undesired systemic activity can be expressed with an L:T ratio, where L stands for the local bioavailability and T stands for the total systemic bioavailability. The L:T ratio depends not only on the ability of the different devices to divide the delivered dose between the lungs and the oropharynx but also on the inherent difference in gastrointestinal (GI) first-pass metabolism between different substances. The L:T ratio should therefore not be used to make comparisons across different drug substances but only to compare the same drug formulated in different inhalation systems. A high L:T ratio expresses a good targeting ability of the combination of substance and device or a low contribution from the GI tract. A high L:T ratio also reflects a more beneficial balance between wanted and unwanted effects. The L:T ratio was calculated from literature data for a number of salbutamol (albuterol) formulations and for two budesonide and two terbutaline formulations. For salbutamol, values ranged from 0.15 to 0.55 with different devices. For budesonide, the values ranged from 0.66 to 0.85, and for terbutaline, the values ranged from 0.59 to 0.79. The L:T ratio can thus be used to aid in the choice of inhaler.