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KMID : 0648320120180030088
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Journal of The Korean Society of Hypertension
2012 Volume.18 No. 3 p.88 ~ p.96
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Pharmacokinetic and Pharmacodynamic Study Determines Factors Affecting Blood Pressure Response to Valsartan
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Cho Jin-Man
Yim Sung-Vin
Jin Hui
Sohn Il-Suk
Hwang Hui-Jeong
Park Chang-Bum
Jin Eun-Sun
Kim Chong-Jin
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Abstract
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Background: Valsartan is an angiotensin II receptor blocker and is used for patient with hypertension. Although response to valsartan varies each individual, there is no study about factors affecting the variability of valsartan response.
Methods: To investigate the effects of valsartan on the baseline characteristics of blood pressure, single group, open label, pre- and postcomparison clinical study was conducted. Total 21 male Korean volunteers were enrolled. Each subject was administered no drugs in first period and valsartan 80 mg (Diovan HCT) in second period. For pharmacodynamic analysis, 24 hours blood pressure changes were monitored by ambulatory blood pressure monitoring. Twenty-four hour blood pressure changes were matched to valsartan concentration and analyzed by correlation analysis. Changes in blood pressure pattern were also analyzed. Subjects were divided into responder, non-responder, and reverse responder according to pre- and post- 24 hours blood monitoring results. For determination of pharmacokinetic parameters, plasma concentration of valsartan was measured by a validated ultra-performance liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters including area under the plasma concentration versus time curve from 0 hour to the last measurable concentration (AUCt), area under the plasma concentration versus time curve extrapolated to infinity, maximum plasma concentration (Cmax), and time required to reach maximum plasma concentration (Tmax) were calculated by noncompartmental models in the BA-CALC 2008 program ver. 1.0.0.
Results: There were no significant associations between blood pressure changes and pharmacokinetic parameters of valsartan. Blood pressure pattern change analysis showed significant results. For AUCt, total amount of absorbed valsartan was 25,808 ± 6,863.0 ng?hr/mL , 20,683 ± 8,782.7 ng?hr/mL, and 12,502 ± 5,566.6 ng?hr/mL in responder, non-responder, and reverse responder, respectively (p = 0.041). In Cmax, maximum concentration of valsartan was 4,314 ± 1,522.6 ng/mL, 2,588 ± 1,273.9 ng/mL, and 2,056 ± 1,075.5 ng/mL, respectively.
Conclusions: These results showed that response to valsartan was not associated with blood concentration in healthy volunteers and changes in blood pressure patterns to valsartan might be associated with the amount of drugs which are absorbed to subjects.
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KEYWORD
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Valsartan, Pharmacokinetics, Pharmacology, Blood pressure monitoring
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