Massive overdoses with sustained-release lithium carbonate preparations: pharmacokinetic model based on two case studies.

Clinically significant delayed absorption after lithium overdose has been reported previously without adequate explanation. We have studied two patients after they took massive intentional lithium overdoses. The first patient presented shortly after ingesting 74 g of lithium carbonate. Pharmacokinetic analysis with a multicompartmental model of 29 serum lithium concentrations during 300 h (including hemodialysis) established absorption and elimination kinetics. Lithium absorption was both slow (peak concentration 33 h after the initial overdose) and delayed (a second peak occurred at 148 h, 30 h after initiation of oral tube feedings). The delayed absorption of a large fraction of lithium implicated a gastrointestinal drug reservoir. Study of the pharmacokinetics in a second patient, who ingested 98 g of lithium carbonate, provided additional evidence of an endogenous reservoir. This patient's medical management was guided by experience gained from the initial case. Appropriate management for a predicted endogenous drug reservoir may have shortened intensive care and hospitalization. In treating overdoses of sustained-release drug preparations, clinically significant delayed absorption triggered by enteral fluids must be considered as a contributor to delayed absorption.