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Pharmacokinetics of digoxin in patients with acute myocardial infarction
Insights
Acute myocardial infarction slows oral digoxin absorption, leading to lower peak serum concentrations in patients compared to healthy individuals. However, the total absorbed dose of digoxin remains unchanged.
Area of Science:
- Pharmacology
- Cardiology
- Clinical Pharmacy
Background:
- Acute myocardial infarction (AMI) can alter drug pharmacokinetics.
- Digoxin is a crucial medication for managing heart failure, but its absorption may be affected by AMI.
Purpose of the Study:
- To investigate the impact of AMI on the pharmacokinetics of orally administered digoxin.
- To compare digoxin absorption and elimination in patients with AMI-induced heart failure versus healthy controls.
Main Methods:
- Oral administration of 0.75 mg digoxin to 12 patients with AMI and 12 healthy controls.
- Measurement of serum digoxin concentrations over 24 hours.
- Analysis of urinary digoxin excretion and renal clearance.
- Correlation analysis with hemodynamic parameters and cardiac enzyme levels.
Main Results:
- Lower initial serum digoxin concentrations and 12-hour area under the concentration-time curve (AUC) in AMI patients (P < 0.01).
- No significant differences in 24-hour AUC, urinary excretion, or renal clearance between groups.
- Correlation of 24-hour AUC with pulmonary capillary wedge pressure and heart rate (P < 0.01).
- Decreased renal clearance linked to elevated MB isoenzyme of creatine kinase (P < 0.001).
- Morphine administration reduced and delayed peak digoxin serum concentrations (P < 0.001).
Conclusions:
- Oral digoxin absorption is slower, resulting in lower peak serum concentrations in patients with AMI compared to healthy subjects.
- Despite altered absorption kinetics, the total amount of digoxin absorbed is not significantly different.
- AMI-related factors, including hemodynamic changes and cardiac enzyme levels, influence digoxin pharmacokinetics.
Abstract:
The effects of acute myocardial infarction on the pharmacokinetics of digoxin were studied. Digoxin, 0.75 mg, was given orally to 12 patients with left-sided cardiac failure due to acute myocardial infarction and to 9 healthy control subjects. Serum concentration of digoxin in the first 4 hours and the area under the serum concentration-time curve in the first 12 hours after administration of the drug were lower in patients with infarction than in control subjects (P less than 0.01). The 24 hour area under the concentration curve, the amount excreted in urine and the renal clearance did not differ between the groups. The 24 hour area under the concentration curve correlated with the predigoxin pulmonary capillary wedge pressure and with heart rate (P less than 0.01). The decrease of renal clearance of digoxin was related to the serum activity of MB isoenzyme of creatine kinase (P less than 0.001). Morphine reduced and delayed the peak serum concentrations of digoxin (P less than 0.001). Thus, the absorption of oral digoxin was slower and the peak concentrations remained lower in patients with acute myocardial infarction than in healthy control subjects. However, the total amount of digoxin absorbed was unchanged.