Use of activated charcoal in a simulated poisoning with acetaminophen: a new loading dose for N-acetylcysteine?
OBJECTIVE
To investigate the ability of a supranormal dose of N-acetylcysteine to overcome the effects of activated charcoal on N-acetylcysteine bioavailability and to determine the effects of activated charcoal on serum acetaminophen levels.


METHODS
Ten healthy adult volunteers participated in a controlled cross-over experiment. During phase I (control), subjects ingested 3 g acetaminophen, followed one hour later by the normal loading dose of N-acetylcysteine (140 mg/kg). During phase II (charcoal), subjects ingested 3 g acetaminophen, followed one hour later by 60 g activated charcoal and a supranormal loading dose of N-acetylcysteine (235 mg/kg).


METHODS
Serum levels of N-acetylcysteine were measured every 30 minutes for six hours. A serum acetaminophen level was measured at four hours.


RESULTS
The area under the curve for N-acetylcysteine was significantly higher for phase II than phase I (P < .05, two-tailed paired t-test). Peak N-acetylcysteine and time to peak were not significantly different. The four-hour serum acetaminophen level was significantly lower for phase II than phase I (P < .05, two-tailed paired t-test). Diarrhea occurred during both phases, but N-acetylcysteine was otherwise well tolerated.


CONCLUSIONS
These results suggest that activated charcoal can be used safely for victims of acetaminophen overdose. A beneficial effect in preventing acetaminophen absorption can be expected if it is given within one hour after ingestion. If N-acetylcysteine is needed because of a toxic serum acetaminophen level, bioavailability can be ensured by increasing the N-acetylcysteine loading dose from 140 mg/kg to 235 mg/kg.
Chamberlain
J M
JM
Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC.
Gorman
R L
RL
Oderda
G M
GM
Klein-Schwartz
W
W
Klein
B L
BL
D000082:Acetaminophen / Q000097:blood / Q000493:pharmacokinetics / Q000506:poisoning*; D000111:Acetylcysteine / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D000284:Administration, Oral; D000327:Adsorption; D000328:Adult; D001682:Biological Availability; D002606:Charcoal / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006261:Headache / Q000139:chemically induced; D006801:Humans; D007408:Intestinal Absorption; D011041:Poisoning / Q000188:drug therapy; D012894:Sleep Stages / Q000187:drug effects; D013997:Time Factors
D002606:Charcoal; D000082:Acetaminophen; D000111:Acetylcysteine