Transl Clin Pharmacol.  2017 Jun;25(2):85-92. 10.12793/tcp.2017.25.2.85.

Pharmacokinetic characteristics of fluticasone, salmeterol and tiotropium after concurrent inhalation

Affiliations
  • 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, Republic of Korea. ijjang@snu.ac.kr
  • 2Hanmi Pharmaceutical Co., Ltd., Seoul 05545, Republic of Korea.

Abstract

Chronic obstructive pulmonary disease (COPD) is a type of progressive, obstructive lung disease characterized by long-term poor airflow. The symptoms of COPD may be relieved and its progression delayed by fluticasone (FTS), salmeterol (SM), and tiotropium (TTP). The aim of this study is to investigate pharmacokinetic (PK) characteristics of inhaled FTS, SM, and TTP after co-administration. An open-label, single-arm, three-period, simple ascending dose study was conducted in 10 healthy male subjects. A single dose of FTS/SM (250/50 µg) and TTP (18 µg) were concomitantly inhaled in period 1, and the dose of each drug was escalated to two- and three-fold in periods 2 and 3, respectively, with a 2-week washout between periods. Activated charcoal was co-administered before and after inhalation to block gastrointestinal absorption. Blood samples for PK analysis were collected up to 24 hours. PK parameters were obtained by non-compartmental analysis. FTS, SM, and TTP rapidly reached maximum plasma concentration after inhalation (0.08-3.00 h, 0.03-0.10 h and 0.03-0.10 h, respectively) and were eliminated with mean half-lives of 9.29-10.44 h, 6.09-12.39 h and 0.25-47.42 h, respectively. PK assessment of the lowest dose of TTP was limited due to relatively low systemic exposure compared to the lower limit of quantification. In conclusion, PK characteristics of FTS, SM, and TTP by pulmonary absorption were evaluated after concurrent inhalation. FTS and SM showed dose-proportional PK profiles between 250-750 µg and 50-150 µg, respectively, while TTP presented dose-proportionality in the early phase exposure between 18-54 µg.

Keyword

Fluticasone; Salmeterol; Tiotropium; Pharmacokinetics; Chronic Obstructive Pulmonary Disease

MeSH Terms

Charcoal
Fluticasone*
Gastrointestinal Absorption
Humans
Inhalation*
Lung Diseases, Obstructive
Male
Pharmacokinetics
Plasma
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Absorption
Salmeterol Xinafoate*
Tiotropium Bromide*
Charcoal
Fluticasone
Salmeterol Xinafoate
Tiotropium Bromide
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