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Massive overdoses with sustained-release lithium carbonate preparations: pharmacokinetic model based on two case
R C Friedberg1, D A Spyker, D A Herold
1University of Virginia Health Sciences Center, Department of Pathology, Charlottesville 22908.
Clinical Chemistry
|July 1, 1991
Summary
Massive lithium overdose can cause delayed absorption due to a gastrointestinal reservoir. This finding highlights the need to consider enteral fluids when managing sustained-release drug overdoses.
Area of Science:
- Toxicology
- Pharmacokinetics
- Clinical Pharmacology
Background:
- Delayed absorption of lithium after overdose is a known phenomenon.
- The underlying mechanisms for this delayed absorption remain inadequately explained.
Observation:
- Two patients with massive intentional lithium carbonate overdoses were studied.
- Pharmacokinetic analysis revealed slow and significantly delayed lithium absorption, with secondary peaks occurring hours after initial ingestion.
- Evidence of an endogenous gastrointestinal drug reservoir was identified as the cause of delayed absorption.
Findings:
- Lithium absorption kinetics were characterized using a multicompartmental model over 300 hours.
- A large fraction of lithium was absorbed slowly, with peak concentrations delayed significantly.
- Enteral fluids, such as those from tube feedings, appeared to trigger the release of lithium from the gastrointestinal reservoir.
Implications:
- Understanding the endogenous drug reservoir is crucial for managing lithium overdose.
- Appropriate management strategies considering this reservoir could potentially shorten intensive care and hospitalization durations.
- Clinicians must consider delayed absorption triggered by enteral fluids when treating overdoses of sustained-release medications.