Development of a population pharmacokinetic model to describe olmesartan medoxomil/hydrochlorothiazide (20/12.5 mg) FDC tablet in male healthy South Korean subjects

Title
Development of a population pharmacokinetic model to describe olmesartan medoxomil/hydrochlorothiazide (20/12.5 mg) FDC tablet in male healthy South Korean subjects
Author(s)
강원구채정우[채정우]백인환[백인환]정상훈[정상훈]백현문[백현문]송병정[송병정]이병요[이병요]윤휘열[윤휘열]권광일[권광일]
Keywords
TO-MODERATE HYPERTENSION; PLACEBO-CONTROLLED TRIAL; COMBINATION THERAPY; BLOOD-PRESSURE; HUMAN PLASMA; DOUBLE-BLIND; HYDROCHLOROTHIAZIDE; MEDOXOMIL; LOSARTAN; MONOTHERAPY
Issue Date
201408
Publisher
DUSTRI-VERLAG DR KARL FEISTLE
Citation
INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS, v.52, no.8, pp.676 - 683
Abstract
Aim: The objective of the present study was to develop population pharmacokinetic models for olmesartan medoxomil and hydrochlorothiazide and to investigate the influence of demographic factors on these population pharmacokinetics. Methods: Plasma concentrations of olmesartan medoxomil and hydrochlorothiazide were measured in 41 healthy volunteers enrolled in our bioequivalence study by LC-MS/MS following oral administration of an olmesartan medoxomil/hydrochlorothiazide (20/12.5 mg) fixed-dose combination tablet. This data and covariates were subjected to nonlinear mixed-effect modeling analysis using the NONMEM software. Evaluation featured a visual predicted check and bootstrapping. Results: The distributions of olmesartan medoxomil and hydrochlorothiazide were best fitted using a two-compartment model with no lag time and first-order elimination. When analyzing hydrochlorothiazide kinetics, we found that TCHO and CL/F were correlated, while HB and K-a influenced olmesartan medoxomil modeling. All evaluations indicated that the pharmacokinetic profiles of olmesartan medoxomil and hydrochlorothiazide were adequately described using our PPK model. Conclusions: This study indicates that demographic factors influence the inter-individual variability in the disposition of the combination drug, and it might be more useful to apply it to the PK of olmesartan medoxomil/hydrochlorothiazide (20/12.5 mg) FDC tablets administered to patients with hypertension.
URI
http://hdl.handle.net/YU.REPOSITORY/31169http://dx.doi.org/10.5414/CP202046
ISSN
0946-1965
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약학대학 > 약학부 > Articles
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