Population Pharmacokinetics of Inhaled Umeclidinium and Vilanterol in Patients with Chronic Obstructive Pulmonary Disease

Abstract

There were no apparent pharmacokinetic interactions when umeclidinium and vilanterol were co-administered in patients with COPD. The effects of patient demographics, including age, bodyweight, and CLCR, on umeclidinium or vilanterol systemic exposure were minimal, and therefore no dose adjustments are necessary.

Long-acting muscarinic antagonists

“…However, when LABAs were compared to tiotropium alone, the risk of myocardial infarction and other MACEs was not greater [128]. Moreover, to date, the risk of MACEs using LABA/LAMA fixed dose combinations is considered to be uncommon, if any [ Pharmacokinetics LAMA bioavailability mainly derives from the lung dose and is substantially proportional to the dose inhaled within the studied dosage ranges [111,[129][130][131]. After inhalation, all LAMAs rapidly reach peak plasma levels.…”

“…Aclidinium is rapidly metabolized by esterases without involvement of cytochrome P450 [129]. Umeclidinium is primarily metabolized into inactive derivatives by CYP2D6 in the liver [131]. However, no accumulation was reported to occur after 7-day administration of umeclidinium 125 mg daily in patients with moderate hepatic impairment [133] or poor CYP2D6 metabolism [131].…”

“…Umeclidinium is primarily metabolized into inactive derivatives by CYP2D6 in the liver [131]. However, no accumulation was reported to occur after 7-day administration of umeclidinium 125 mg daily in patients with moderate hepatic impairment [133] or poor CYP2D6 metabolism [131]. To date, the potential for drug interactions between LAMAs and other drugs in COPD patients is considered to be low [111,[129][130][131].…”

“…However, no accumulation was reported to occur after 7-day administration of umeclidinium 125 mg daily in patients with moderate hepatic impairment [133] or poor CYP2D6 metabolism [131]. To date, the potential for drug interactions between LAMAs and other drugs in COPD patients is considered to be low [111,[129][130][131]. Coadministration of LAMA and LABA does not seem to affect the PK of either drug consistently at steady state [111,[129][130][131].…”

A Randomized, Crossover Study to Investigate the Pharmacokinetics and Safety of Inhaled Fluticasone Furoate and Umeclidinium, Administered Separately and in Combination via Dry Powder Inhaler in Healthy Adult Volunteers

“…A limitation of the present study is the lack of Hispanic/Latino representation, as differences in systemic exposure compared with subjects of other ethnicities could not be investigated. However, further data will be collected in larger, Phase III studies.The impact of patient demographics and baseline characteristics (including gender and ethnicity) on UMEC systemic exposure has been studied using population PK modeling, based on pooled PK data from two large Phase III studies[26]. The results demonstrated no significant impact of gender or ethnicity on UMEC PK following inhalation of UMECmonotherapy, or the combination of UMEC with the LABA VI.…”