The Use of Cholecystokinin as an Adjunctive Treatment for Toxin Ingestion

• Published in: Journal of toxicology. Clinical toxicology 2004, Vol.42 (1), p.61-66
• Main Authors: Hofbauer, Randall D., Holger, Joel S.
• Format: Article
• Language: English
• Subjects: Acetaminophen - pharmacokinetics; Acetaminophen - poisoning; Activated charcoal; Adjuvants, Pharmaceutic - therapeutic use; Analgesics, Non-Narcotic - pharmacokinetics; Analgesics, Non-Narcotic - poisoning; Animals; Area Under Curve; Biological and medical sciences; Charcoal - therapeutic use; Cholecystokinin; Cholecystokinin - therapeutic use; Dogs; Dose-Response Relationship, Drug; Drug intoxications. Doping; Gastrointestinal Agents - therapeutic use; Medical sciences; Pharmacology. Drug treatments; Poisoning - drug therapy; Single-Blind Method; Subtoxic acetaminophen
• ISSN: 0731-3810; 1097-9875
• DOI: 10.1081/CLT-120028746

Study Objective: To determine if pharmacologic trapping of ingested toxins in the stomach using cholecystokinin (CCK) in addition to activated charcoal (AC) decreases the absorption of ingested toxins. Methods: We performed a two-phase study that was prospective, randomized, blinded, and placebo-controlled, using a subtoxic acetaminophen (APAP) animal model. Eight adult beagle dogs were studied to detect a 20% decrease in 4h APAP levels with a power of 80%. A control arm using APAP at 100 mg kg without AC or CCK was first performed. APAP levels were drawn at 0.5, 1, 1.5, 2, 4, 8, and 24h. This was repeated in a CCK dose finding phase using a 60-min CCK infusion (4 vs. 8 pmol kg min) starting at 30 min post-APAP ingestion. Once the optimal CCK dose was established, animals in the treatment phase received AC and a 1h infusion of CCK (vs. placebo). The efficacy of CCK when started at 30 and 60 min post-APAP ingestion was tested. Results: In the dose finding arm 8 pmol kg min was well tolerated and also reduced maximum APAP levels by a mean of 49% from control. This dose was then used for the treatment phase. Four-hour APAP levels, maximum APAP levels, and area under the curve (AUC) were measured. No significant differences were found between placebo and CCK arms at either the 30 or 60 min postingestion interventions. Conclusions: In this model, CCK infusion did not decrease the absorption of APAP. Adding charcoal to the model overcame the suggested beneficial effect of CCK alone in the dosing arm.