Simulated gastric fluid (SGF) at pH 1.2 and simulated intestinal fluid (SIF) at pH 6.8 were prepared according to the JP XVII. Purified water was prepared by Smart2Pure (Thermo Fisher Scientific K.K., Tokyo, Japan). The filters used qualitative filter paper and cellulose acetate membrane filters (Advantec, Tokyo, Japan). The Plus shaker EP-1 (Taitec, Saitama, Japan), the Thermo minder SM-05N (Taitec), and the pH meter F-52 (Horiba, Kyoto, Japan) were used. All other chemicals or solvents were of analytical grades. (Tokyo, Japan), Wako Pure Chemical Corporation (Osaka, Japan), Ayumi Pharmaceutical Corporation (Tokyo, Japan), and Bachem AG (Bubendorf, Switzerland), respectively. Medicinal carbon powder, NAC, NAC oral solution 17.6%, and N,N’-diacetyl-L-cystine (DAC) were obtained from Nichi-Iko Pharmaceutical Co., Ltd. The objective of this study was to evaluate the effect of AC on a 72-h oral regimen of NAC using in vitro methods. 11, 12 ) If AC stays in the stomach and intestines, the NAC would likely be adsorbed onto the AC. 10 ) However, the transit time of AC is several hours, even though a cathartic is given with the AC to enhance the elimination of the charcoal-poisoning complex. Although the evidence is not clear, it is recommended in the package insert that NAC should be administered at least 1 h after AC has been given to avoid decreasing the absorption of NAC. 8 ) In their study, the protocol did not include AC treatment because AC would decrease the absorption of NAC. Rumack and Peterson reported the 72-h oral NAC regimen approved by the FDA. It should be started as soon as possible but is effective within 8–24 h after APAP ingestion. 8 ) The earlier the administration of NAC, the greater the likelihood of preventing hepatotoxicity. 6, 7 ) It is approved for a 72-h oral regimen, with a loading dose of 140 mg/kg, followed by 70 mg/kg every 4 h, for an additional 17 doses. It is a precursor of glutathione (GSH) that detoxifies N-acetyl -p-benzoquinone imine (NAPQI), a highly reactive intermediate from APAP. NAC is used as a specific antidote for APAP overdose to help prevent liver injury. It is also important in N-acetylcysteine (NAC) therapy. Because APAP overdose causes liver injury and often death in severe cases, it is important that AC is administered soon after APAP ingestion as a first treatment. It is also a common agent in drug overdoses due to its availability in over-the-counter preparations. 2 – 5 ) APAP is commonly used as an antipyretic and an analgesic. It is well known that AC is an effective agent for acetaminophen (APAP) overdose. If AC is given within 60 min after ingestion, its efficacy is significantly increased. Many studies have demonstrated the ability of AC adsorption in vitro and reducing bioavailability in vivo. It is widely used for accidental or intentional ingestion of these substances as a first-line treatment. By both the actions of adsorption and oxidation, AC may reduce the effect of loading and maintenance doses of NAC.Īctivated charcoal (AC) is an adsorbent that can adsorb a variety of drugs, poisons, and chemicals. The rate of conversion to DAC was higher in the SIF than that in the SGF. The residual rate in the SGF was 2.1%, and that in the SIF was 0.3%. We also determined whether or not AC could adsorb the loading and maintenance doses of NAC after APAP adsorption. The actual Qm based on only the amount of adsorption in the SGF was 294 mg/g, and that in the SIF was 59 mg/g. The apparent Qm based on the amount of decreased NAC in the SGF was 400 mg/g, and that in the SIF was 714 mg/g. We then calculated the maximum adsorption capacity per gram of AC ( Qm). This revealed that NAC was not only adsorbed onto the AC but also converted to N,N’-diacetyl-L-cystine (DAC), which is oxidized NAC. The AC was then removed by filtration, and the NAC concentration was determined. Different concentrations of NAC solution diluted with simulated gastric fluids (SGF) and simulated intestinal fluids (SIF) were added to AC and incubated at 37☌ for 1 h. We evaluated AC adsorption of NAC after APAP adsorption in vitro. NAC is a specific antidote for APAP overdose and administered as a 72-h oral regimen. Because AC adsorbs a wide variety of toxins, it may also adsorb the oral antidote, N-acetylcysteine (NAC). Gastrointestinal decontamination by activated charcoal (AC) is the most important treatment for acetaminophen (APAP) overdose.
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