Pharmacokinetic analysis of inhaled salmeterol in asthma patients: Evidence from two dry powder inhalers
| Autor: | Vangelis Karalis, Panos Macheras, Konstantina Soulele |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Adult
Male Agonist medicine.drug_class Population Pharmaceutical Science Pharmacology Bioequivalence 030226 pharmacology & pharmacy Young Adult 03 medical and health sciences 0302 clinical medicine Bolus (medicine) Pharmacokinetics Administration Inhalation medicine Humans Pharmacology (medical) education Adrenergic beta-2 Receptor Agonists Salmeterol Xinafoate Asthma Volume of distribution education.field_of_study Cross-Over Studies business.industry Dry Powder Inhalers General Medicine Middle Aged respiratory system medicine.disease Bronchodilator Agents respiratory tract diseases Therapeutic Equivalency 030228 respiratory system Female Salmeterol business medicine.drug |
| Zdroj: | Biopharmaceutics & Drug Disposition. 38:407-419 |
| ISSN: | 0142-2782 |
| Popis: | Salmeterol (SAL) is a long-acting β2-adrenergic agonist, which is widely used in the therapy of asthma. The aim of this study was to investigate the pharmacokinetics (PK) of inhaled salmeterol 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-time (C-t) data were initially analysed using classic non-compartmental PK approaches, while the main objective of the study was to apply population PK modeling. The relative fraction of the dose absorbed via the lungs (RL ) was set as a parameter in the structural model. The plasma C-t profiles of salmeterol 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 an i.v. bolus) was found to describe successfully the C-t profiles of salmeterol. The estimated RL value was 13% suggesting a high gut deposition of inhaled salmeterol. Women were found to exert less capability to eliminate salmeterol than men, while body weight (in allometric form) was found to be an important covariate on the peripheral volume of distribution. |
| Databáze: | OpenAIRE |
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