Does a Soft Drink Mixture Improve Tolerance of Activated Charcoal in the Adult Poisoned Patient Without Affecting Efficacy: A Randomized Crossover Trial
Phase: PHASE4
Conditions: Overdose
Sponsor: State University of New York - Upstate Medical University

 
Title: Does a soft drink mixture improve tolerance of activated charcoal in an 
adult without affecting efficacy: A randomized controlled crossover study 
 
Clinical Trials Number: NCT06219967 
 
Document Date: 11/28/22 

Background 
Activated charcoal has become an established component of gastrointestinal 
decontamination in the poisoned patient.1 While the exact methods vary by manufacturer, 
the basic production process involves pyrolysis of organic material followed by exposure to 
an oxidizing gas at high temperature.2 This results in a compound with a very large surface 
area – 800-1200 m2/g.3 Charcoal as a compound has been around for thousands of years, 
being used for heating and cooking for thousands of years.4 The compounds ability to 
adsorb chemicals gradually began to be known. In 1773 organic chemist Carl Wilhelm 
Scheele used charcoal to absorb gases. In 1830, a French pharmacist named Touery 
survived after swallowing a lethal dose of strychnine with charcoal to prove its ability to 
adsorb poisons.    
The eLicacy of charcoal, though historically debated, has become rather well 
established. It has become a staple in the management of the poisoned patient. Numerous 
studies have proven that activated charcoal administration decreases the adsorption of 
xenobiotic from the gut in an overdose.4-10 These have been done in both volunteer subjects 
and in poisoned patients. In addition, some studies have gone beyond simply looking at 
pharmacokinetic data and have looked at clinical outcome data. Although a detailed 
review of the literature is beyond the scope of this background section, several studies will 
be brieﬂy reviewed here. In a study by Christophersen et al, healthy volunteers were given a 
sub-toxic dose of acetaminophen.5 They discovered that charcoal signiﬁcantly reduced the 
amount of acetaminophen absorbed from the gut when given at both 1 hour post-ingestion 
and 2 hours post-ingestion. However, the reduction was less signiﬁcant when charcoal was 
given 2 hours post-ingestion compared to one hour post-ingestion, emphasizing the need 
to administer charcoal as early as possible post-ingestion. Another study by Yeates and 
Thomas looked at healthy volunteers given a sub-toxic dose of acetaminophen with 
charcoal administered at 1, 2, or 4 hours post-ingestion. They found a signiﬁcant reduction 
in absorption of acetaminophen when charcoal was given 1 or 2 hours post-ingestion, but 
not 4 hours.6 A study by Isbister et al looked at patients after intentional ingestion of 
citalopram.7 They found that charcoal those that received charcoal were less likely to 
experience a prolonged QT on EKG. Finally, a study by Underhill et al looked at patients 
presenting after an intentional ingestion of acetaminophen and randomized them to 
diLerent methods of GI decontamination: gastric lavage, activated charcoal, ipecacuanha, 
or no decontamination. They found that activated charcoal was the most eLective 
decontamination method.8  
Despite the apparent beneﬁt of activated charcoal, one of the main limitations to its 
use is its taste and appearance. As such, numerous studies have looked at diLerent 
mixtures to try to improve the taste/appearance of the charcoal.12-15 The results of these 
studies are mixed, but, for the most part, ﬁnd that charcoal is better received if it is mixed in 

something like cola or chocolate milk. However, the caveat is that some of these vehicles 
used to improve the palatability of the charcoal may decrease its ability to adsorb 
xenobiotic. Ice cream has been found to decrease the eLicacy of the charcoal.16 Jam has 
been found to not aLect the eLicacy of the charcoal.17 Chocolate syrup has had mixed 
resulted.18-19 Yogurt was found to not aLect the eLicacy of the charcoal in vivo but did aLect 
the eLicacy in vitro.15  
Despite several taste test studies looking at the eLects of cola in improvement in 
palatability of charcoal, there does not appear to be any studies looking to see if cola 
aLects the eLicacy of charcoal. This is likely the most likely mixture in the Emergency 
Department as soft drinks are readily available in the patient nourishment supplies. 
In addition, there are no studies to our knowledge looking at comparison between 
clear and opaque containers in charcoal tolerance. There also are not any randomized 
controlled trials in poisoned patients. This study will be a pilot study to demonstrate that 
mixing charcoal with cola does not aLect the eLicacy of the charcoal, allowing us to 
continue on to the randomized controlled trial.  
 
References  
1. Smith SW, Howland M. Activated Charcoal. In: Nelson LS, Howland M, Lewin NA, Smith 
SW, Goldfrank LR, HoLman RS. Eds. Goldfrank’s Toxicologic Emergencies, 11e New York, 
NY: McGraw-Hill. 
2. 
Paddock Laboratories LRLPC. Actidose-Aqua & Actidose ® with Sorbitol. Actidose ® 
with Sorbitol. Actidose ®-Aqua. Activated Charcoal Suspension [product label]. 
Minneapolis, MN: Paddock Laboratories, LLC; 2014.  
3. 
Olson KR. Activated Charcoal for acute poisoning: one toxicologist’s journey. J Med 
Toxicol. 2010;6:190-198.  
4. 
Olson KR. Activated charcoal for acute poisoning: one toxicologist’s journey. J Med 
Toxicol. 2010; 6:190-198. 
5. 
Marketos SG, Androutsos G. Charcoal: from antiquity to artiﬁcial kidney. J Nephrol. 
2004;17:453-456.  
6. 
Christophersen AB, Levin D, Hoegberg LCG, Angelo HR, Kampmann JP. Activated 
charcoal alone or after gastric lavage: a simulated large paracetamol intoxication. Br J Clin 
Pharmacol. 2002;53:312-317 
7. 
Yeates PJA and Thomas SHL. ELectiveness of delayed activated charcoal 
administration in simulated paracetamol (acetaminophen) overdose. Br J Clin Pharmacol. 
2000;49:1-14.  
8. 
Isblster GK, Friberg LE, Stokes B, Buckley NA, Lee C, Gunja N, Brown SG, 
MacDonald E, Graudlins A, Holdgate A, DuLull SB. Activated charcoal decreases the risk of 

QT prolongation after citalopram overdose. Annals of Emergency Medicine. 
2007;50(5):593-600. 
9. 
Underhill TJ, Greene MK, Dove AF. A comparison of the eLicacy of gastric lavage, 
ipecacuanha, and activated charcoal in the emergency management of paracetamol 
overdose. Archives of Emergency Medicine. 1990. 7:148-154. 
10. 
Buckley NA, Whyte IM, O’Connell DL, Dawson AH. Activated charcoal reduces the 
need for N-acetylcysteine treatment after acetaminophen (paracetamol) overdose. Clinical 
Toxicology 1999;37(6):753-757. 
11. 
Friberg LE, Isbister GK, DuLull SB. Pharmacokinetic-pharmacodynamic modelling 
of QT interval prolongation following citalopram overdoses. Br J Clin Pharmacol. 
2005;61(2):177-190. 
12. 
Cheng A, Ratnapalan S. Improving the palatability of activated charcoal in pediatric 
patients. Pediatric Emergency Care. 2007;23(6):384-386. 
13. 
Dagnone D, Matsui D, Rieder MJ. Assessment of the palatability of vehicles for 
activated charcoal in pediatric volunteers. Pediatric Emergency Care. 2002;18(1):19-21. 
14. 
Skokan EG, Junkins EP, Corneli HM. Taste test: children rate ﬂavoring agents used 
with activated charcoal. Arch Pediatr Adolesc Med. 2001;155(6):683-686.  
15. 
Hoegberg LCG, Christophersen AB, Christensen HR, Angelo HR. Comparison of the 
adsorption capacities of an activated-charcoal-yogurt mixture versus activated-charcoal-
water slurry in vivo and in vitro. Clinical Toxicology. 2005;43:269-275. 
16. 
Levy G, Soda DM, Lampman TA. Inhibition by ice cream of the antidotal eLicacy of 
activated charcoal. Amer J Hosp Pharm. 1975;32:289-291.  
17. 
Neve, RE. Antidotal eLicacy of activated charcoal in presence of jam, startch, and 
milk. Am J Hosp Pharm. 1976;33:965-966.  
18. 
Scholtz EC, JaLe JM, Colaizzi JL. Evaluation of ﬁve activated charcoal formulations 
for inhibition of aspirin absorption and palatability in man. Am J Hosp Pharm. 
1978;35:1355-1359. 
19. 
Navarro KR, Krenzelok EP. Relative eLicacy and palatability of three activated 
charcoal mixtures. Veterinary and human toxicology. 1980;22(1):6-9. 
 
Protocol:  
 
Recruitment: 5 subjects will be recruited through ﬂyers and word of mouth.  
 
Inclusion: Healthy non-pregnant adults ages 18-40 
 
Exclusion: 
• Self-reported history of any hepatic, gastrointestinal, or renal disease. 

• Self-reported history of alcohol or drug abuse (deﬁned as any use of illicit drugs, 
alcohol use greater than the CDC standard recommended amount of 2 drinks per 
day in men). 
• Any current daily prescription medication use 
• Any allergy to Tylenol 
• Pregnant women 
• Age <18 or >40 
• Any gluten allergy or intolerance  
• Weight <60 kg or >93 kg 
• Prisoners 
• Adults unable to consent 
 
Participants will be provided the inclusion and exclusion criteria when they contact an 
investigator about the study.  Inclusion/exclusion criteria are conﬁrmed and documented at 
each protocol visit. We will use a screening questionnaire to access potential subjects 
based on the inclusion/exclusion criteria 
 
Settings 
The Clinical Research Unit in the Institute for Human Performance will be used to conduct the 
study. For screening, discussion of private information will be performed over the phone from a 
private office in the Poison Control Center.  
 
Study Day Method/Procedure: 
 
Visit 1  
a. This will be done over the phone from a private office in the Poison Control 
Center 
b. Will review inclusion/exclusion criteria to look at eligibility 
c. If done in person, will obtain signed consent  
 
The following will be collected at the start of visit 2 
a. Age 
b. Weight measured 
Visit 2 and 3 
a. If not already signed on visit 1, consent forms will be signed before 
initiation of the study 

b. Participants will be told in advance not to consume any alcohol the day 
before, day of, or day after the experiment 
c. Women will complete a pregnancy test on arrival to ensure exclusion 
criteria are not met.  
d. Participants will be told in advance not use consume and products 
containing acetaminophen the 5 days before, day of, and 5 days after the 
experiment 
e. Participants arrive at 8 AM after an overnight fast to have commenced at 
4am. They will have refrained from using acetaminophen for 5 days prior 
to the study. 
f. Participants will have their age and weight measured.  
g. Subjects will be fed a light breakfast of 2 pieces of dry toast and 200 mL of 
water 
h. A peripheral IV will be placed in the antecubital fossa for blood draws 
i. Area will be cleaned with an alcohol wipe 
ii. Tourniquet will be placed on the arm proximal to planned IV 
insertion site 
iii. IV tubing will be prepped with a saline flush 
iv. Vein will be accessed with an angiocath IV catheter (needle size 
determined by the nurse) 
v. Prepped IV tubing will be connected to the catheter and the line 
will be secured to the skin with a tegaderm.  
i. Acetaminophen ingestion will occur 1 hour after completion of the 
breakfast 
i. 45 mg/kg acetaminophen will be administered with 150 mL of 
water. The number of tablets will be rounded down to the nearest 
whole number 
ii. 325 mg tablets will be utilized to increase the gut burden of tablets 
to more closely mimic the overdose setting. The number of tablets 
will be rounded down to the nearest whole number 
iii. A max weight of 93 kg will be set for the participants. With this 
max weight, a participant at the max weight of 93 kg would be 
expected to ingest 4185 mg of Tylenol. However, as we are 
rounding down to the nearest tablet, they would only ingest 3,900 
mg of Tylenol, below the 4g recommended daily limit. 
j. Subjects will consume the charcoal mixture 1 hour after consumption of 
the acetaminophen tablets. Using a random number generator, 
participants will be assigned to either the control charcoal of the soda-
charcoal mix for the first experimental day. 

i. For the control day, 50 g activated charcoal will be administered 
by itself. Actidose-aqua, a pre-mixed charcoal-water slurry, will be 
used 
ii. For the study day, 50 g activated charcoal (Actidose-aqua) will be 
administered as a mixture with 240 cc soft drink (1:1 charcoal to 
soft drink). Actidose-aqua will be used  
k. Subjects will rate the appearance, smell, flavor, texture, and overall 
appeal of the charcoal mixture on a 1-10 scale, 10 being the best and 1 
being the worst. 
l. Blood for acetaminophen assay will be drawn in a Gold or Mint tube 
(approximately 5 mL per tube) at 0, 15, 30, 45, 60, 75, 90, 120, 180, 240, 
minutes 
i. Samples will be taken to the lab for processing 
ii. Samples will be run using Abbott’s Acetaminophen L3K assays 
(enzymatic colometric assay) 
m. Subjects will receive a light snack of crackers and water no sooner than 3 
hours after the charcoal is consumed (4 hours after acetaminophen was 
ingested).  
n. Participants will be reminded to refrain from using acetaminophen for 5 
days after the study 
 
Statistical Analysis 
DiLerences in all measures on the palatability questionnaire will be analyzed using a paired 
sample t-test with 95% conﬁdence intervals.   
 
To analyze diLerences in the pharmacokinetics between the study arms, the area under the 
curve, time of maximum concentration, and maximum concentration will be obtained. 
Area under the curve is used as a marker of drug absorption and will be calculated utilizing 
the trapezoidal rule. A paired t-test will be performed for comparison with 95% conﬁdence 
intervals.   
 
To compare the mg/kg dosing of acetaminophen for each arm of the study, a paired sample t-test 
will be performed. 
 
All analysis will be conducted using  IBM SPSS Version 26. The level of signiﬁcance was set 
at a p-value <0.05.