Development of a population pharmacokinetic model to describe olmesartan medoxomil/ hydrochlorothiazide (20/12.5 mg) FDC tablet in male healthy South Korean subjects.
OBJECTIVE
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 Ka 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. *These two authors contributed equally to this work.
Jung-Woo
JW
Chae
In-Hwan
IH
Baek
Jeong-Won
JW
Seo
Sang-Hoon
SH
Jung
Hyun-Moon
HM
Back
Byung-Jeong
BJ
Song
Byung-Yo
BY
Lee
Hwi-Yeol
HY
Yun
Wonku
W
Kang
Kwang-Il
KI
Kwon
D000284:Administration, Oral; D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid / Q000379:methods; D018592:Cross-Over Studies; D004338:Drug Combinations; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007093:Imidazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008954:Models, Biological; D017711:Nonlinear Dynamics; D000068557:Olmesartan Medoxomil; D056910:Republic of Korea; D013607:Tablets; D053719:Tandem Mass Spectrometry / Q000379:methods; D013777:Tetrazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency; D055815:Young Adult
D000959:Antihypertensive Agents; D004338:Drug Combinations; D007093:Imidazoles; D013607:Tablets; D013777:Tetrazoles; D006852:Hydrochlorothiazide; D000068557:Olmesartan Medoxomil