Pharmacokinetics of diltiazem in massive overdose

Several cases of poisoning with diltiazem have been described in the literature, but information about the pharmacokinetics of diltiazem in overdose is sparse. The authors report pharmacokinetic and clinical observations in a patient who ingested 7.2 g of slow-release dilitiazem. Grave, persistent hypotension was the overriding clinical manifestation, but the patient eventually survived with aggressive cardiovascular support. No serious conduction abnormalities were seen. Blood samples were taken repeatedly for 2-3 days for analysis of serum diltiazem and desacetyldiltiazem and desacetyldiltiazem concentrations. The serum diltiazem concentration measured in the first sample taken (16.5 h postingestion), 3,171 ng/ml, is one of the highest concentrations reported in a patient who survived. The half-life was 13.3 h for diltiazem and 10.5 h for desacetyldiltiazem. Charcoal hemoperfusion had no apparent effect on the elimination of either compound. The relatively long half-life of diltiazem may have resulted from rate-limiting absorption and probably does not indicate saturation of diltiazem metabolism. The patient was discharged with no apparent neurological or cardiological deficits.