Devender Kodati1, Harish Kaushik Kotakonda2, Narsimhareddy Yellu3. 1. Department of Pharmacology and DMPK, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, Telangana, 506009, India. 2. Department of Pharmacy, IST, JNTUH, Hyderabad, Telangana, India. 3. Department of Pharmacology and DMPK, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, Telangana, 506009, India. ynrucpsc@gmail.com.
Abstract
BACKGROUND: Olmesartan medoxomil is an orally given angiotensin II receptor antagonist indicated for the treatment of hypertension. OBJECTIVE: The aim of the study was to establish a population pharmacokinetic model for olmesartan, the active metabolite of olmesartan medoxomil, in Indian hypertensive patients, and to evaluate effects of covariates on the volume of distribution (V/F) and oral clearance (CL/F) of olmesartan. METHODS: The population pharmacokinetic model for olmesartan was developed using Phoenix NLME 1.3 with a non-linear mixed-effect model. Bootstrap and visual predictive check were used simultaneously to validate the final population pharmacokinetic models. The covariates included age, sex, body surface area (BSA), bodyweight, height, creatinine clearance (CLCR) as an index of renal function and liver parameters as indices of hepatic function. RESULTS: A total of 205 olmesartan plasma sample concentrations from 69 patients with hypertension were collected in this study. The pharmacokinetic data of olmesartan was well described by a two-compartment linear pharmacokinetic model with first-order absorption and an absorption lag-time. The mean values of CL/F and V/F of olmesartan in the patients were 0.31565 L/h and 44.5162 L, respectively. Analysis of covariates showed that age and CLCR were factors influencing the clearance of olmesartan and the volume of distribution of olmesartan was dependent on age and BSA. CONCLUSION: The final population pharmacokinetic model was demonstrated to be appropriate and effective and it can be used to assess the pharmacokinetic parameters of olmesartan in Indian patients with hypertension.
BACKGROUND:Olmesartanmedoxomil is an orally given angiotensin II receptor antagonist indicated for the treatment of hypertension. OBJECTIVE: The aim of the study was to establish a population pharmacokinetic model for olmesartan, the active metabolite of olmesartanmedoxomil, in Indian hypertensivepatients, and to evaluate effects of covariates on the volume of distribution (V/F) and oral clearance (CL/F) of olmesartan. METHODS: The population pharmacokinetic model for olmesartan was developed using Phoenix NLME 1.3 with a non-linear mixed-effect model. Bootstrap and visual predictive check were used simultaneously to validate the final population pharmacokinetic models. The covariates included age, sex, body surface area (BSA), bodyweight, height, creatinine clearance (CLCR) as an index of renal function and liver parameters as indices of hepatic function. RESULTS: A total of 205 olmesartan plasma sample concentrations from 69 patients with hypertension were collected in this study. The pharmacokinetic data of olmesartan was well described by a two-compartment linear pharmacokinetic model with first-order absorption and an absorption lag-time. The mean values of CL/F and V/F of olmesartan in the patients were 0.31565 L/h and 44.5162 L, respectively. Analysis of covariates showed that age and CLCR were factors influencing the clearance of olmesartan and the volume of distribution of olmesartan was dependent on age and BSA. CONCLUSION: The final population pharmacokinetic model was demonstrated to be appropriate and effective and it can be used to assess the pharmacokinetic parameters of olmesartan in Indian patients with hypertension.
Authors: D E Salazar; S H Song; J Shi; S Rohatagi; R Heyrman; D R Wada; T J Carrothers Journal: Clin Pharmacol Ther Date: 2011-12-28 Impact factor: 6.875
Authors: T Pene Dumitrescu; T Anic-Milic; K Oreskovic; J Padovan; K L R Brouwer; P Zuo; V D Schmith Journal: Antimicrob Agents Chemother Date: 2013-04-29 Impact factor: 5.191
Authors: L Marthey; G Cadiot; P Seksik; P Pouderoux; J Lacroute; F Skinazi; B Mesnard; J A Chayvialle; G Savoye; A Druez; D Parlier; V Abitbol; M Gompel; M Eoche; E Poncin; R Bobichon; P Colardelle; P Wils; H Salloum; S Peschard; F Zerbib; B Méresse; N Cerf-Bensussan; G Malamut; F Carbonnel Journal: Aliment Pharmacol Ther Date: 2014-09-09 Impact factor: 8.171
Authors: Veenu Bala; Yashpal S Chhonker; Abdullah Alshehri; Constant Edi; Catherine M Bjerum; Benjamin G Koudou; Christopher L King; Daryl J Murry Journal: Antimicrob Agents Chemother Date: 2021-07-26 Impact factor: 5.938