Pharmacokinetic Analysis of Inhaled Salmeterol in Asthma Patients: Evidence from Two Dry Powder Inhalers

ABSTRACT Salmeterol (SAL) is a long‐acting β2‐adrenergic agonist, which is widely used in the asthma therapy. The aim of this study was to investigate the pharmacokinetics (PK) of inhaled SAL in asthma patients using two different dry powder inhalers. This analysis was based on data from 45 subjects who participated in a two‐sequence, four period crossover bioequivalence (BE) study after single administration of the test (T) and reference (R) products. In order to mimic more closely the real treatment conditions, activated charcoal was not co‐administered. Plasma concentration (C) – time (t) data were initially analyzed using classic non‐compartmental PK approaches, while the main objective of the study was to apply population PK modeling. The relative fraction of dose absorbed via the lungs (RL) was set as a parameter in the structural model. The plasma C‐t profiles of SAL showed a biphasic time course indicating a parallel pulmonary and gastrointestinal (GI) absorption. A two‐compartment disposition model with first order absorption from the GI and very rapid absorption from lungs (like IV bolus) was found to describe successfully the C‐t profiles of SAL. The estimated RL value was 13% suggesting a high gut deposition of inhaled SAL. Women were found to exert less capability to eliminate SAL than men, while body weight (in allometric form) was found to be an important covariate on peripheral volume of distribution.
Source: Biopharmaceutics and Drug Disposition - Category: Drugs & Pharmacology Authors: Tags: ORIGINAL PAPER Source Type: research