Lack of ethnic differences of moxifloxacin and metabolite pharmacokinetics in East Asian men.
J Pharmacokinet Pharmacodyn
; 45(2): 199-214, 2018 04.
Article
em En
| MEDLINE
| ID: mdl-29170990
ABSTRACT
This study was designed to investigate ethnic differences in the pharmacokinetics (PKs) of moxifloxacin and its metabolites, M1 (sulfo conjugate) and M2 (acyl-glucuronate), among Japanese, Chinese, and Korean populations, following oral administration. We used a population PK modeling approach using data from a clinical study involving 79 healthy male volunteers. A comprehensive population PK model considering the PK mechanism of moxifloxacin and its metabolites was newly built. The structures of the final model were two-compartment for moxifloxacin and one-compartment for M1 and M2, with first-order absorption with lag time for all three compounds. The formation of M1 and M2 from moxifloxacin via a first-pass effect and subsequent metabolic clearance in the system were also modeled. Lean body mass on the central volume of distribution (V c ) and estimated glomerular filtration rate on renal clearance (CL r ) were identified as covariates of PKs of moxifloxacin. Additionally, bioavailability was slightly higher in Koreans, whereas CL r , non-renal clearance (CL nr ), and V c were slightly lower. Regarding M1 and M2, body surface area on CL r of M2 and UGT1A1*6 on F of M2 were modeled. Korean ethnicity was observed to influence CL nr of M2, F of M2, and the metabolic clearance of moxifloxacin to M2. However, the exposure levels of moxifloxacin, M1, and M2 in Koreans were comparable to those in Japanese and Chinese because the effects of Korean ethnicity on some PK parameters were counterbalanced. These results suggest that PKs for moxifloxacin and its metabolites among East Asian populations are essentially similar.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Moxifloxacina
Limite:
Adult
/
Humans
/
Male
Idioma:
En
Revista:
J Pharmacokinet Pharmacodyn
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Japão