| 1. |
- Isbister, Geoffrey K., et al.
(författare)
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Activated charcoal decreases the risk of QT prolongation after citalopram overdose
- 2007
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Ingår i: Annals of Emergency Medicine. - : Elsevier BV. - 0196-0644 .- 1097-6760. ; 50:5, s. 593-600
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Tidskriftsartikel (refereegranskat)abstract
- Study objective: We determine whether single-dose activated charcoal (SDAC) administration after citalopram overdose reduces the proportion of patients developing abnormal QT prolongation. Methods: Data were collected retrospectively for citalopram overdose patients presenting to 8 emergency departments. Demographics, dose, coingested drugs, SDAC administration, and serial ECGs were extracted from medical records. The primary outcome was the proportion of patients who had an observed QT,RR combination at any time above an abnormal threshold, established as a predictor of torsade de pointes. We compared the proportion of patients with QT prolongation who received or did not receive SDAC. These data were analyzed within a Bayesian framework, using probabilities of abnormal QT,RR combinations with and without derived from a previous single-center study. WinBUGS was used to generate posterior estimates and credible intervals of the relative risk by combining the prior probabilities and the study data. Results: SDAC was administered on average 2.1 hours (range, 0.5 to 6.25 hours) after ingestion in 48 of 254 admissions, and abnormal QT,RR combinations occurred in 2 cases (4.2%), compared with 23 of 206 (11.2%) cases not receiving SDAC. There did not appear to be any clinically important difference in age, sex, dose, and cardiotoxic coingestants between the 2 groups. No cases of torsade de pointes occurred. The estimated relative risk of having an abnormal QT,RR combination for SDAC compared to no SDAC was 0.28 (0.06 to 0.70) (median with 2.5% and 97.5% credible limits). The probability that the relative risk was less than 1.0 was 0.99, which can be interpreted as very strong evidence in favor of a beneficial effect of SDAC. The absolute risk difference was estimated as 7.5% and the median number needed to treat as 13.3. Conclusion: SDAC may be effective in reducing the risk of a prolonged QT in patients after citalopram overdose. Current trends toward nonuse of activated charcoal should be evaluated to determine whether patients poisoned by specific agents may benefit from activated charcoal administration.
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| 2. |
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| 3. |
- Isbister, Geoffrey K, et al.
(författare)
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Human methyl parathion poisoning
- 2007
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Ingår i: Clinical Toxicology. - : Informa UK Limited. - 1556-3650 .- 1556-9519. ; 45:8, s. 956-960
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Tidskriftsartikel (refereegranskat)abstract
- Background. Methyl parathion is classed as an extremely hazardous pesticide with a rodent LD50 of 6 to 24 mg/kg. It has been banned in numerous countries, but there are few reports of acute methyl parathion poisoning. Methods. Plasma cholinesterase and acetylcholinesterase were measured in blood. Methyl parathion and the major metabolite 4-nitrophenol where measured in serum and urine. Based on the available concentration-time data, the pharmacokinetic parameters of methyl parathion were estimated for this patient. Case Report and Results. A 29-year-old male ingested 50 to 100mL (12 to 24 g) of methyl parathion causing delayed and prolonged suppression of acetylcholinesterase but almost no clinical effects. Absorption was predicted to last for 30 hours and the bioavailability appeared to be very low. Conclusions. Although it is feasible the patient ingested much less, a tenth of his alleged ingestion dose is more than the oral LD50 in rats. Methyl parathion appears to be less toxic in humans than parathion for similar amounts ingested, which is not consistent with the two pesticides having similar rodent LD50.
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| 4. |
- Isbister, G. K., et al.
(författare)
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Pharmacokinetics of quetiapine in overdose and the effect of activated charcoal
- 2007
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Ingår i: Clinical Pharmacology and Therapeutics. - : Springer Science and Business Media LLC. - 0009-9236 .- 1532-6535. ; 81:6, s. 821-827
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to investigate the pharmacokinetics of quetiapine overdose and the effect of charcoal. The data set included 204 concentration-time points from 54 quetiapine overdose events (median dose 2,700 mg (300-24,000 mg)). Charcoal was administered 0.5-6 h after 19 overdoses. A fully Bayesian methodology for population pharmacokinetic analysis was used and data were modelled using WinBUGS. Uncertainty in the dose history was considered in model building by estimating dose amount and dose time within a possible range. Inclusion of informative priors stabilized the model and population parameter values could be estimated well. A one-compartment model with first-order input and first-order elimination described the data. The final model included uncertainty in dose time. The median and interquartile range of the half-life for individual patients was 6.6 h (4.9-8.4 h). Charcoal was estimated to reduce fraction absorbed by 35%. Co-ingested CYP3A4 inhibitors appeared to decrease clearance and CYP3A4 inducers increase clearance. Charcoal administration may be beneficial after quetiapine overdose.
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| 5. |
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| 6. |
- Kumar, V V P, et al.
(författare)
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The effect of decontamination procedures on the pharmacokinetics of venlafaxine in overdose
- 2009
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Ingår i: Clinical Pharmacology and Therapeutics. - : Springer Science and Business Media LLC. - 0009-9236 .- 1532-6535. ; 86:4, s. 403-410
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this work was to investigate the pharmacokinetics (PK) of venlafaxine in overdose and the effects of single-dose activated charcoal (SDAC) and whole-bowel irrigation (WBI), alone or in combination, as methods of decontamination. The data included 339 concentration-time points from 76 venlafaxine overdose events (median dose 2,625 (150-13,500 mg)); 69 were slow-release doses. SDAC, WBI, a combination of both, or no decontamination were administered to patients as decided by the treating clinician. The data were modeled using WinBUGS (Windows Bayesian Inference Using Gibbs Sampling). A one-compartment model with first-order input and elimination provided an adequate description of the data. SDAC increased clearance (CL) of venlafaxine by 35%, and SDAC and WBI combined reduced the fraction absorbed by 29%. However, the latter produced a greater reduction in maximum plasma concentration (C(max)) for a similar drop in area under the plasma concentration-time curve (AUC). Both SDAC alone, and a combination of SDAC and WBI, decreased the AUC after venlafaxine overdose, but the combination may be more beneficial because it reduces peak concentrations to a greater extent.
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