Document Detail


Pharmacokinetics and pharmacodynamics of benidipine using a slow receptor-binding model.
MedLine Citation:
PMID:  16336286     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: This study examined the relationship between the plasma concentration of benidipine, a long-lasting antihypertensive agent with Ca(2+)-channel-blocking properties, and its cardiovascular effects (reduction in blood pressure and increase in heart rate) in order to assess the usefulness of pharmacokinetic-pharmacodynamic (PK-PD) modelling in describing this relationship. METHODS: Two groups of 24 healthy volunteers received either a 4- or 8-mg benidipine hydrochloride tablet; 11 additional subjects received a placebo. Serial blood sampling and PD measurements were performed over 8 h thereafter. Plasma concentrations of benidipine were measured with a validated LC/MS/MS system, and the effects on blood pressure and heart rate were assessed during the same period. A two-compartment open model with lag time was used to explain the PK properties, and the PD model was characterized by slow receptor binding, reflecting the binding of benidipine to the ion-channel receptor. RESULTS: Benidipine reached mean peak plasma concentrations of 1.04 and 3.85 ng/mL at 0.5 and 0.75 h after 4 and 8 mg doses, respectively. Peak cardiovascular effects were detected approximately 2 h after the administration of either dose. Maximal decreases in diastolic blood pressure with 4 and 8 mg of benidipine were 7.79 and 14.75 mmHg, respectively, and maximal increases in heart rate were 7.32 and 17.56 bpm, respectively. No significant changes in systolic blood pressure were observed. The cardiovascular effects were analysed according to a slow receptor-binding model. CONCLUSIONS: The tested PK-PD model successfully described the relationship between the plasma concentration of benidipine and its cardiovascular effects.
Authors:
H-Y Yun; M-H Yun; W Kang; K-I Kwon
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Publication Detail:
Type:  Clinical Trial; Journal Article    
Journal Detail:
Title:  Journal of clinical pharmacy and therapeutics     Volume:  30     ISSN:  0269-4727     ISO Abbreviation:  J Clin Pharm Ther     Publication Date:  2005 Dec 
Date Detail:
Created Date:  2005-12-12     Completed Date:  2006-03-17     Revised Date:  2008-05-28    
Medline Journal Info:
Nlm Unique ID:  8704308     Medline TA:  J Clin Pharm Ther     Country:  England    
Other Details:
Languages:  eng     Pagination:  541-7     Citation Subset:  IM    
Affiliation:
College of Pharmacy, Chungnam National University, Daejeon, Korea.
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MeSH Terms
Descriptor/Qualifier:
Adult
Blood Pressure / drug effects
Calcium Channel Blockers / blood,  pharmacokinetics*,  pharmacology*
Calcium Channels / metabolism
Dihydropyridines / blood,  pharmacokinetics*,  pharmacology*
Heart Rate / drug effects
Humans
Models, Biological*
Vasodilator Agents / blood,  pharmacokinetics,  pharmacology
Chemical
Reg. No./Substance:
0/Calcium Channel Blockers; 0/Calcium Channels; 0/Dihydropyridines; 0/Vasodilator Agents; 105979-17-7/benidipine

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