Quetiapine in overdosage: a clinical and pharmacokinetic analysis of 14 cases.

Data on quetiapine overdosage are only sparsely available in the literature. This study provides additional data on the pharmacokinetics and clinical effects of intoxication with this atypical antipsychotic drug. The authors performed a retrospective analysis of all quetiapine intoxications reported to and screened by the toxicological laboratory of the Central Hospital Pharmacy The Hague between January 1999 and December 2003. Cases with known suggested amount of intake and medical outcome were included. From the patient's medical record and from the toxicological laboratory findings, patient demographic characteristics (gender, age), details of quetiapine intoxication (estimated time of ingestion, estimated amount of ingestion, and coingested drugs) and clinical parameters were obtained. Severity of intoxication was graded by the Poisoning Severity Score (PSS). Individual pharmacokinetic parameter values were calculated using a one-compartment open model and a Bayesian fitting procedure. Out of a total of 21 intoxications with quetiapine, 14 fulfilled the inclusion criteria. The ingested dose ranged from 1200 to 18,000 mg. The blood concentration ranged from 1.1 to 8.8 mg/L with a lag time of 1 to 26.2 hours between time of ingestion and blood sampling at the emergency ward. The most frequent findings were somnolence and tachycardia. The PSS was minor in 6 patients (43%), moderate in 5 patients (36%), and severe in 3 patients (21%). Severity of intoxication was not associated with a higher amount of quetiapine intake. The authors found no correlation between the serum concentration of quetiapine and the amount ingested. Elimination t(1/2) was not prolonged. It can be concluded that quetiapine intoxications appear to proceed mildly. Tachycardia and somnolence were the main clinical symptoms in our case series. No fatalities occurred. The severity of clinical symptoms was not associated with either a high serum concentration or the suggested amount ingested of quetiapine.

Pattern of 72-hour intragastric acidity in a homogeneous group of intensive care unit patients.

To gain insight into the variation over time of gastric acidity in postoperative ICU patients, intragastric pH was prospectively studied in patients undergoing elective abdominal aortic reconstructive surgery during a 72-hr intra- and postoperative period. Intragastric pH was monitored continuously in 14 patients with combined glass electrodes. During the day of surgery (day 1), the median 24-hr pH for all patients was 6.25 (5.8-7.0, IQR). However, three of the 14 studied patients had a median 24-hr pH of 1.8. The median 24-hr pH throughout day 2 for all was 2.45 (1.6-4.7, P = 0.001). The median 24-hr pH on day 3 was 1.6 (1.5-2.1, P = 0.001). Median 8-hr pH values demonstrate a remarkable interpatient and intraindividual variation in the course of the postoperative period. A progressive lowering of the intragastric pH was observed in the first 40 hr. From the 40- to 48-hr interval until the end of the study, no further significant decrease was found. The intragastric pH was above 4, 74% of the time during day 1, 39% during day 2 (P = 0.006) and 16% during day 3 (P = 0.003). Percentage of time above 4 on day 2 was significantly higher than on day 3 (P = 0.04). In conclusion, since gastric acid and pepsin seem to play a role in stress ulceration, this study suggests some patients are at risk of stress ulceration from the beginning of surgery, but most patients become at risk of stress ulceration in the course of the postoperative period.

The Reflotron Total Cholesterol assay in heparinized venous and capillary blood.

We recently evaluated the Reflotron Total Cholesterol dry chemistry assay by examining the calibration and the accuracy of the assay in serum, whole venous EDTA-blood and capillary EDTA blood. We now describe a study on the analysis in heparinized venous and heparinized finger stick blood. Cholesterol assays in venous serum and plasma, and in finger capillary blood and plasma (all with heparin) were compared. Finger capillary blood was obtained in two ways: 1. in heparinized capillaries; 2. in a Becton Dickinson microtainer that could be centrifuged for separation of the plasma. Venous blood was obtained in plain tubes (for serum) and heparinized tubes to obtain venous whole blood and also venous plasma. We did not, on average, find large differences between the concentrations of cholesterol in the various materials. The regression equations for finger capillary whole blood and venous whole blood however show higher slopes than the others. Inaccuracy due to the sampling technique appears to be no greater for finger capillary samples than for venous samples.