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Kinetic-dynamic relations and individual responses to enalapril
R Donnelly1, P A Meredith, H L Elliott
1University Department of Medicine and Therapeutics, Stobhill General Hospital, Glasgow, United Kingdom.
Hypertension (Dallas, Tex. : 1979)
|March 1, 1990
Summary
Individual responses to enalapril, an angiotensin converting enzyme inhibitor, vary due to pharmacokinetic and pharmacodynamic factors. Higher pretreatment blood pressure correlated with greater blood pressure reduction, indicating personalized treatment approaches for essential hypertension.
Area of Science:
- Pharmacology
- Cardiovascular Medicine
- Hypertension Research
Background:
- Interindividual variability in antihypertensive drug response is significant.
- Angiotensin converting enzyme (ACE) inhibitors, like enalapril, show diverse patient responses.
- Understanding factors influencing enalapril efficacy is crucial for managing essential hypertension.
Purpose of the Study:
- To investigate factors determining individual responses to enalapril in patients with essential hypertension.
- To characterize the pharmacokinetic-dynamic relationship of enalapril.
- To correlate patient characteristics with enalapril's efficacy.
Main Methods:
- A placebo-controlled study involving 13 subjects with essential hypertension.
- Utilized an integrated kinetic-dynamic model with a parameter for saturable protein binding.
- Measured blood pressure reduction and plasma ACE activity inhibition over time.
Main Results:
- Individual enalaprilat concentrations correlated with blood pressure reduction and ACE inhibition.
- Group Emax for systolic and diastolic blood pressure reduction was -46.1 and -19.7 mm Hg, respectively.
- No correlation found between responsiveness and age or plasma renin activity, but a positive correlation with pretreatment blood pressure.
Conclusions:
- Individual patient factors, particularly pretreatment blood pressure, significantly influence enalapril's antihypertensive effect.
- The study highlights the importance of personalized dosing and response assessment for ACE inhibitors.
- Kinetic-dynamic modeling provides valuable insights into enalapril's variability in essential hypertension.