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Diltiazem concentrations in plasma vs PR intervals on electrocardiogram in 8 men
1Centre of Metabolism & Pharmacokinetics, China Pharmaceutical University, Nanjing, China.
Zhongguo Yao Li Xue Bao = Acta Pharmacologica Sinica
|September 1, 1996
Summary
This study developed an acute tolerant model to describe the relationship between diltiazem (Dil) plasma concentrations and PR interval changes on ECG in men. The model effectively characterized diltiazem pharmacokinetics and pharmacodynamics.
Area of Science:
- Pharmacology
- Clinical Pharmacology
- Cardiology
Background:
- Diltiazem is a calcium channel blocker used to treat cardiovascular conditions.
- Understanding the relationship between diltiazem concentration and its effect on cardiac conduction is crucial for safe and effective dosing.
Purpose of the Study:
- To develop and validate an acute tolerant model to describe the relationship between plasma diltiazem concentrations and PR interval changes on ECG in men.
- To characterize the pharmacokinetic and pharmacodynamic parameters of diltiazem in healthy male subjects.
Main Methods:
- A single oral dose of 90 mg diltiazem was administered to 8 healthy men.
- Plasma diltiazem concentrations and ECG parameters (PR interval) were simultaneously measured.
- A two-compartmental pharmacokinetic model and an acute tolerant pharmacodynamic model were applied.
Main Results:
- A two-compartmental model accurately described diltiazem plasma concentrations with estimated parameters (e.g., t1/2 beta: 5.9 h, MRT: 15.9 h).
- The acute tolerant model effectively fitted the plasma concentration-effect data, yielding pharmacodynamic parameters (e.g., S: 829 s.g-1.L, T50: 10 µg.L-1).
Conclusions:
- An acute tolerant model successfully described the relationship between diltiazem plasma concentrations and PR interval changes in men.
- This model provides a valuable tool for understanding diltiazem's cardiac effects and optimizing its therapeutic use.