Effect of activated charcoal on the pharmacokinetics of pholcodine, with special reference to delayed charcoal ingestion.
We conducted a randomized study with four parallel groups to investigate the effect of single and multiple doses of activated charcoal on the absorption and elimination of pholcodine administered in a cough syrup. The first group received 100 mg of pholcodine on an empty stomach with water only (control); the second group took 25 g of activated charcoal immediately after pholcodine; the third group received 25 g of activated charcoal 2 h and the fourth group 5 h after ingestion of the 100-mg dose of pholcodine. In addition, the fourth group received multiple doses (10 g each) of charcoal every 12 h for 84 h. Blood samples were collected for 96 h and urine for 72 h. Pholcodine concentrations were measured by high-performance liquid chromatography. A significant reduction in absorption was found when charcoal was administered immediately after pholcodine; the AUC0-96h was reduced by 91% (p < 0.0005), the Cmax by 77% (p < 0.0005), and the amount of pholcodine excreted into urine by 85% (p < 0.0005). When charcoal was administered 2 h after pholcodine, the AUC0-96h was reduced by 26% (p = 0.002), the Cmax by 23% (p = NS), and the urinary excretion by 28% (p = 0.004). When administered 5 h after pholcodine, charcoal produced only a 17% reduction in the AUC0-96h (p = 0.06), but reduced the further absorption of pholcodine still present in the gastrointestinal tract at the time of charcoal administration, as measured by AUC5-96h (p = 0.006). Repeated administration of charcoal failed to accelerate the elimination of pholcodine. We conclude that activated charcoal is effective in preventing the absorption of pholcodine, and its administration can be beneficial even several hours after pholcodine ingestion.
Laine
K
K
Department of Pharmacology and Clinical Pharmacology, University of Turku, Finland.
Kivistö
K T
KT
Ojala-Karlsson
P
P
Neuvonen
P J
PJ
D000328:Adult; D000931:Antidotes / Q000008:administration & dosage / Q000494:pharmacology*; D000996:Antitussive Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D019540:Area Under Curve; D002606:Charcoal / Q000008:administration & dosage / Q000494:pharmacology*; D003061:Codeine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D005260:Female; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D009025:Morpholines / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D013997:Time Factors
D000931:Antidotes; D000996:Antitussive Agents; D009025:Morpholines; D002606:Charcoal; C008872:pholcodine; D003061:Codeine