Influence of activated charcoal on the pharmacokinetics and the clinical features of carbamazepine poisoning

Brahmi, Nozha; Kouraichi, Nadia; Thabet, H.; Amamou, M.

doi:10.1016/j.ajem.2005.12.025

Cited by 46 publications

(26 citation statements)

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“…A randomized trial of ten patients who overdosed on phenobarbital reported a profound reduction in serum phenobarbital half-life, but no change in time on mechanical ventilation or the time in the hospital between those receiving a single dose of AC or MDAC [100]. In contrast, 12 patients with confirmed carbamazepine poisonings were randomized to receive MDAC or a single dose of AC [101]. Though peak carbamazepine levels were similar, the duration of coma was significantly decreased ( P = 0.02) as were the hours on mechanical ventilation ( P = 0.001) and the length of hospital stay ( P = 0.00001) with MDAC.…”

Section: Introductionmentioning

confidence: 99%

Gastrointestinal decontamination in the acutely poisoned patient

et al. 2011

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ObjectiveTo define the role of gastrointestinal (GI) decontamination of the poisoned patient.Data SourcesA computer-based PubMed/MEDLINE search of the literature on GI decontamination in the poisoned patient with cross referencing of sources.Study Selection and Data ExtractionClinical, animal and in vitro studies were reviewed for clinical relevance to GI decontamination of the poisoned patient.Data SynthesisThe literature suggests that previously, widely used, aggressive approaches including the use of ipecac syrup, gastric lavage, and cathartics are now rarely recommended. Whole bowel irrigation is still often recommended for slow-release drugs, metals, and patients who "pack" or "stuff" foreign bodies filled with drugs of abuse, but with little quality data to support it. Activated charcoal (AC), single or multiple doses, was also a previous mainstay of GI decontamination, but the utility of AC is now recognized to be limited and more time dependent than previously practiced. These recommendations have resulted in several treatment guidelines that are mostly based on retrospective analysis, animal studies or small case series, and rarely based on randomized clinical trials.ConclusionsThe current literature supports limited use of GI decontamination of the poisoned patient.

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Section: Introductionmentioning

confidence: 99%

Gastrointestinal decontamination in the acutely poisoned patient

et al. 2011

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“…For patients presenting with or eventually absorbing enough to have excessive concentrations, enhancing elimination via multiple doses of activated charcoal (MDAC) has proven to reduce enterohepatic recirculation of carbamazepine and thus reduce elimination half-lives. 7 Repeated doses of AC also have the capacity to clean or mop the gut of concretions and bezoars that may be responsible for the erratic absorption. 8 In rare and severe poisoning, because carbamazepine is amendable to hemodialysis, aggressive enhancement of elimination via this technique may also be entertained.…”

Section: Discussionmentioning

confidence: 99%

Delayed Elevation in Carbamazepine Concentrations After Overdose

Patel

Schindlbeck

Bryant

2013

American Journal of Therapeutics

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An initial carbamazepine concentration may initially be supratherapeutic, therapeutic, or even subtherapeutic only to persist to rise over time. The aim of this study was to report the frequency of toxic carbamazepine concentrations continuing to rise and to estimate how often an initially therapeutic or subtherapeutic concentration misrepresents the potential toxicity of an acute carbamazepine overdose. An 8-year retrospective search of all carbamazepine exposures reported to the Illinois Poison Center (January 1, 2001 through December 31, 2008) was reviewed. Inclusion criteria were acute poisonings with a documented carbamazepine concentration of >12 μg/mL at any time. Those with initial concentrations of >12 μg/mL that subsequently increased over time were recorded. Additionally, those cases that initially had therapeutic (4-12 μg/mL) or subtherapeutic (<4 μg/mL) concentration were identified. Descriptive statistics were used to analyze the data. A total of 1424 cases were reported. Of the 523 patients with documented concentrations of >12 μg/mL, 93 patients (17.8%) had initial carbamazepine concentrations >12 μg/mL and continued to rise. Sixteen patients (3.5%) had initial carbamazepine concentrations that were therapeutic (4-12 μg/mL) and 7 patients (1.3%) had initial carbamazepine concentrations <4 μg/mL before rising >12 μg/mL. Certain patients had progressive decreases in level of consciousness corresponding to increasing carbamazepine concentrations. Additionally, several patients with initial levels of therapeutic or subtherapeutic concentration later became comatose and required ventilator management. Initial serum carbamazepine concentrations can be misleading. Serial measurements documenting a declining carbamazepine concentration or prolonged observation are recommended when managing these overdoses.

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“…It is unquestionable that carbamazepine is one of the few poisons for which there are conclusive answers about the effectiveness of activated charcoal both in preventing absorption and improving clinical condition that are based on evident clinical studies [16,[31][32][33].…”

Section: Discussionmentioning

confidence: 99%

“…Hence, we felt it timely to study the quantity of seromucosal transport, excretion into bile and urine and some pharmacokinetic parameters of 14 C-carbamazepine after intravenous administration to rats. As a recent publication clearly affirms the effectiveness of multiple-dose activated charcoal treatment of carbamazepine poisoning in human beings anew [16], we were especially interested in an additional effect of orally administered activated charcoal to increase the clearance of seromucosally transported carbamazepine.…”

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confidence: 99%

Seromucosal Transport of Intravenously Administered Carbamazepine Is Not Enhanced by Oral Doses of Activated Charcoal in Rats

Eyer¹,

Jung²,

Neuberger³

et al. 2008

Basic Clin Pharma Tox

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Abstract:The fate of carbamazepine after intravenous injection in rats (n = 24) and the influence of activated charcoal on the kinetics was investigated. After randomization to four groups (n = 6, each), plasma concentration and the quantities of carbamazepine and metabolites excreted into bile, urine and intestine were determined using an in situ perfusion model of the small intestine (Ringer's solution) with or without orally administered activated charcoal (AC + ; AC-) and with or without bile duct cannulation (BD + ; BD -). The cumulative amount of carbamazepine and metabolites exsorbed into the small intestine within 3.5 hr after intravenous injection was about 15% in BD -animals and about 3% in BD + animals. About 20% of the dose was detected in the externalized bile. Activated charcoal did not influence the amount exsorbed into the small intestine. Terminal half-life in plasma ranged from 159 min. to 194 min. within the four treatment groups without statistical significant difference (P = 0.751). Correspondingly, the area under the curve did not vary significantly and ranged between 1.13 and 1.41 g/min./l (P = 0.378). Excretion of carbamazepine and metabolites into urine varied between 3% and 6% of dose within all groups and showed close correlation with diuresis. In an identical experimental approach using a 2-fold intestinal perfusion rate (50 ml/hr; n = 8), no fundamental changes compared to the main experiment regarding pharmacokinetics of carbamazepine were observed. The lack of effect of activated charcoal on the elimination of carbamazepine and metabolites must be contributed to the small amount of the drug being exsorbed into the intestine and may be further influenced by reduced intestinal permeability of carbamazepine and metabolites or inadequate luminal stirring.Activated charcoal is a widely used and generally accepted agent to prevent the absorption of orally ingested drugs, especially in the overdose setting. Although there are no satisfactorily designed clinical studies assessing the benefit from single-dose activated charcoal to recommend this therapy [1], data from literature clearly support the use of multipledose activated charcoal for some toxins such as carbamazepine, dapson, phenobarbital, quinine and theophylline in the case of overdose [2]. Besides the prevention of drug absorption and the possibility of activated charcoal interrupting the enteroenteric circulation, oral administration has also been demonstrated to enhance the clearance of intravenously administered drugs that are exsorbed seromucosally into the intestinal lumen in rats [3][4][5][6][7][8][9][10][11][12]. This process is generally called 'gastrointestinal dialysis' since it was first described in 1982 [13]. Basic pharmacokinetic requirements for clinically relevant seromucosal transport include small size of molecule, intermediate lipophilicity, low protein binding and a small volume of distribution.If a relevant amount of drug would be exsorbed into the intestinal lumen and if orally administered activated charcoa...

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Influence of activated charcoal on the pharmacokinetics and the clinical features of carbamazepine poisoning

Cited by 46 publications

References 12 publications

Gastrointestinal decontamination in the acutely poisoned patient

Gastrointestinal decontamination in the acutely poisoned patient

Delayed Elevation in Carbamazepine Concentrations After Overdose

Seromucosal Transport of Intravenously Administered Carbamazepine Is Not Enhanced by Oral Doses of Activated Charcoal in Rats

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