Pharmacokinetics of beta2-sympathomimetics at the example of fenoterol and conclusion for the administration.

ABSTRACT

The pharmacokinetics of fenoterol (salbutamol, terbutaline) after systemic administration (i.v., infusion, nasal administration) can be best described by a three-compartmental model. Nasal administration causes an effect-time profile between that of infusion and inhalation. The effects of nasal administration on the lung function and the heart rate depend on the plasma levels of the beta2-agonist. The absorption rate after inhalation differs individually in a large variability (1-27% of the dosage). After inhalation the effect on the lung function does not depend on the absorption rate nor on the plasma levels of the beta2-agonist. After inhalation the effect on the lung function is three- to fivefold more expressed than predictable from the plasma level. From the pk/pd data it can be assumed, that there are 10-20 fold higher concentrations in the airways than in the plasma. It is assumed that there are structures nearby the beta2-receptor responsible for the long-lasting effect observed after inhalation. These depot structures cannot be reached from the plasma in concentrations needed for bronchodilation under in vivo conditions. In respect to the effect/side effect relations, there is no doubt that inhalation is the optimal solution for administering beta2-agonists. In respect to the effect/side effect relations more frequent administration of small doses seems to be more favourable than high doses inhaled in long periods.