Pharmacokinetics of multiple inhaled NVA237 doses in patients with chronic obstructive pulmonary disease (COPD).
Int J Clin Pharmacol Ther
; 50(2): 118-28, 2012 Feb.
Article
em En
| MEDLINE
| ID: mdl-22257577
ABSTRACT
OBJECTIVE:
NVA237 (glycopyrronium bromide) is a once-daily longacting muscarinic antagonist (LAMA) in development for the treatment of chronic obstructive pulmonary disease (COPD). This study investigated the pharmacokinetics (PK) of NVA237 following single and repeated once-daily inhalation in mild-tomoderate COPD patients.METHODS:
In this double-blind, parallel-group study, COPD patients were randomized to a 14-day treatment with NVA237 (25, 50, 100 or 200 µg) or placebo. Plasma concentration-time profiles and urinary excretion of NVA237 were determined on Days 1 and 14.RESULTS:
The median time to reach maximal plasma concentration (tmax) was 5 or 6.5 min postinhalation. At steady state (Day 14), total and maximum systemic exposure (AUC0-24, Cmax) to NVA237 and urinary excretion of unchanged drug (Ae0-24) was approximately dose proportional over the 50 - 200 µg dose range. The average exposure was 1.4- to 1.7- fold higher on Day 14 compared with Day 1. The mean terminal elimination half-life (t1/2) of NVA237 ranged between 13 and 22 h. Steady-state plasma concentrations were reached within 1 week of treatment. Renal clearance (CLR) was similar across doses both after single and repeated dosing, ranging between 17.4 and 20.6 l/h. Urinary excretion of NVA237 enantiomers ([3S,2R]- and [3R,2S]-stereoisomers) was similar with respect to the amount excreted within 24 h and the excretion rate.CONCLUSIONS:
The pharmacokinetics of NVA237 were consistent between doses with limited systemic accumulation at steady state after repeated once-daily inhalation.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antagonistas Muscarínicos
/
Doença Pulmonar Obstrutiva Crônica
/
Glicopirrolato
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Int J Clin Pharmacol Ther
Assunto da revista:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Suíça