Activated charcoal alone and followed by whole-bowel irrigation in preventing the absorption of sustained-release drugs

Lapatto‐Reiniluoto, Outi; Kivistö, Kari T.; Neuvonen, Pertti J.

doi:10.1067/mcp.2001.118184

Cited by 28 publications

(22 citation statements)

References 16 publications

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“…Whole bowel irrigation demonstrated the greatest reduction in salicylic acid AUC compared to AC ( P < 0.05) and was associated with fewer adverse effects [49]. In another study, nine healthy patients received sustained-release preparations of carbamazepine, theophylline and verapamil followed 1 h later by AC, AC with WBI or water (control) [50]. Activated charcoal reduced the absorption as measured by the serum AUC by 62%-75% for all three drugs compared to control, but the addition of WBI to the AC actually significantly ( P < 0.01) reduced the efficacy of the AC with carbamazepine (AC, 62% reduction in AUC vs. WBI/AC, 41% reduction in AUC).…”

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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“…A study using therapeutic doses of sustainedrelease carbamazepine, theophylline and verapamil designed to determine whether there was an additive effect of WBI upon charcoal failed to demonstrate such an effect and WBI significantly decreased the effect of charcoal upon one of these three drugs (carbamazepine). However, this study is difficult to interpret because of the small doses of the ingested drugs and because the duration and total volume of WBI were less than in other studies (19).…”

Section: Volunteer Studiesmentioning

confidence: 92%

“…Lapatto-Reiniluoto et al (19) have examined whether whole-bowel irrigation affects the efficacy of charcoal (25 g) on the prevention of the absorption of therapeutic doses of carbamazepine, theophylline and verapamil given one hour earlier as sustained-release tablets in 9 healthy subjects in a randomized crossover study. Whole-bowel irrigation did not increase significantly the effect of charcoal on any absorption parameters [area under the plasma drug concentration-time curve from time zero to 24 hours AUC(0 -24), peak plasma concentration (C max ), C max minus the plasma concentration at 1 hour (CD), time to peak (t max )] of the 3 drugs studied.…”

Section: Effect Of Wbi On Activated Charcoal Efficacymentioning

confidence: 99%

Position Paper: Whole Bowel Irrigation

Toxicologists¹

2004

Journal of Toxicology: Clinical Toxicology

119

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Whole bowel irrigation (WBI) should not be used routinely in the management of the poisoned patient. Although some volunteer studies have shown substantial decreases in the bioavailability of ingested drugs, no controlled clinical trials have been performed and there is no conclusive evidence that WBI improves the outcome of the poisoned patient. Based on volunteer studies, WBI should be considered for potentially toxic ingestions of sustained-release or enteric-coated drugs particularly for those patients presenting greater than two hours after drug ingestion. WBI should be considered for patients who have ingested substantial amounts of iron as the morbidity is high and there is a lack of other options for gastrointestinal decontamination. The use of WBI for the removal of ingested packets of illicit drugs is also a potential indication. WBI is contraindicated in patients with bowel obstruction, perforation, ileus, and in patients with hemodynamic instability or compromised unprotected airways. WBI should be used cautiously in debilitated patients or in patients with medical conditions that may be further compromised by its use. The concurrent administration of activated charcoal and WBI may decrease the effectiveness of the charcoal. The clinical relevance of this interaction is uncertain. A review of the literature since the preparation of the 1997 Whole Bowel Irrigation Position Statement revealed no new evidence that would require a revision of the conclusions of the Statement.

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“…Charcoal prevented the absorption of carbamazepine very effectively, even when started 10 hr after ingestion [30]. In the publication by Lapatto-Reiniluoto, the authors reported a reduction of absorption of carbamazepine (measured as the AUC 0-24 ) by activated charcoal of 62% [31]. In another publication, the absorption of 400 mg oral carbamazepine was decreased greatly (90%) by activated charcoal [32].…”

Section: Discussionmentioning

confidence: 90%

“…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%

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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Activated charcoal alone and followed by whole-bowel irrigation in preventing the absorption of sustained-release drugs

Cited by 28 publications

References 16 publications

Gastrointestinal decontamination in the acutely poisoned patient

Gastrointestinal decontamination in the acutely poisoned patient

Position Paper: Whole Bowel Irrigation

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

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