PHARMACOKINETICS OF DILTIAZEM IN MASSIVE OVERDOSE

Several cases of poisoning with diltiazem have been described in the l iterature, but information about the pharmacokinetics of diltiazem in overdose is sparse. The authors report pharmacokinetic and clinical ob servations in a patient who ingested 7.2 g of slow-release diltiazem. Grave, persistent hypotension was the overriding clinical manifestatio n, 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 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 survi ved. The half-life was 13.3 h for diltiazem and 10.5 h for desacetyldi ltiazem. Charcoal hemoperfusion had no apparent effect on the eliminat ion of either compound. The relatively long half-life of diltiazem may have resulted from rate-limiting absorption and probably does not ind icate saturation of diltiazem metabolism. The patient was discharged w ith no apparent neurological or cardiological deficits.