Evaluating the potential role of oral activated charcoal as an adjunct treatment for severe bacterial infections/malaria

Lead Research Organisation: MRC Unit, The Gambia

Abstract

In Africa, severe malaria or pneumonia, sepsis or neonatal pneumonia account for ca. 46% of the 4.4 million yearly deaths in under 5 year olds. Pre-clinical studies performed in mice suggest that oral activated charcoal can reduce mortality caused by these pathogens. Given that activated charcoal is a licensed, inexpensive drug, blessed with an endless shelf life, that can be given orally or via a naso-gastric tube at high doses without major side effects, we would like to explore its potentially life-saving properties in clinical trials.||However, oral activated charcoal is also known to reduce the blood levels of several drugs including quinine, which is currently the mainstay of specific treatment for severe malaria.||To date, nothing is known about possible interactions between charcoal and artesunate, a highly effective alternative treatment for severe malaria.||Before testing adjuvant treatment with charcoal in cases of malaria, we need to find out if charcoal given orally reduces the drug levels of artesunate given intravenously. For this purpose, we plan to do a study where healthy volunteers receive intravenous artesunate with or without prior or subsequent administration of oral charcoal. On repeated occasions after drug administration a small blood sample will be taken and the levels of artesunate and its active metabolites will be measured.||If we find that oral charcoal does not significantly reduce the levels of artesunate, this would warrant further studies in people with mild, and subsequently severe disease, to see if adding charcoal to the treatment is of benefit.

Technical Summary

In Africa, severe malaria or pneumonia, sepsis or neonatal pneumonia account for ca. 46% of the 4.4 million yearly deaths in under 5 year olds. Exciting new work in mice demonstrates that oral administration of activated charcoal (AC) improves survival in LPS-induced endotoxemia, during sepsis and cerebral malaria (Ulloa et al, de Souza et al., submitted). Given that AC is a licensed, inexpensive drug that can be given orally or via a naso-gastric tube at high doses as a safe therapy of oral poisoning without major side effects we would like to explore its potentially life-saving properties in clinical trials in The Gambia.||Prior to evaluating the potentially exciting effects of oral charcoal, there is a need to study the pharmacokinetics of co-administration of charcoal and the specific drugs: Despite the data being scarce, oral activated charcoal is officially recommended to treat quinine intoxication, as it appears to increase elimination of this drug. No pharmacological data are available assessing the impact of oral activated charcoal when given together with artemisinin derivatives or commonly used antibiotics.||In an open labelled, controlled pharmacokinetic trial, we therefore propose to study co-administration of AC, initially with artesunate in Gambians aged 21-45 years that volunteer for the trial. Subsequent studies will assess this approach in mild cases of malaria and will be expanded to bacterial infections that require treatment with commonly used antibiotics to explore a possible impact of AC on the pharmacokinetics of these drugs.||Blood samples will be taken prior and following drug administration at regularly timed intervals from an indwelling forearm catheter and plasma frozen. The samples will be shipped on dry ice to the London School of Hygiene & Tropical Medicine where drug levels would be analysed using Liquid chromatography / Mass Spectometry (LC/MS) for artesunate and dihydroartesunate to determine the kinetics with and without adjuvant AC treatment.
 
Description Collaboration with mouse immunologists in York and clinical scientists at MRC 
Organisation University of York
Country United Kingdom 
Sector Academic/University 
PI Contribution we conducted the clinical phase 1 trial to evaluate pharmacokinetic interactions of charcoal and I.v. artesunate
Collaborator Contribution The data from the animal studies have been provided to inform our study in humans
Impact study is finished, and a joint ms describing the work on animals and our clinical study is currently under review, An MRC DCS grant application to perform the next steps has been submitted this September. This project is finished now
Start Year 2007