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dc.contributor.authorLi, Yu Kwan-
dc.contributor.authorLam, Ka Fung-
dc.contributor.authorWong, Cheung Lun William-
dc.contributor.authorWong, Anselm Y-
dc.identifier.citationClinical Toxicology 2020; 58(9): 900-906-
dc.description.abstractObjectives: There have been few studies of pharmacobezoar formation, but they can be an important contributor to overdose toxicity. Pharmacobezoars may explain the delayed peak or "double hump" pharmacokinetics, which were noted in previous case reports with delayed toxicity of acetaminophen (APAP). We validated the presence of APAP bezoar formation in a controlled modified in vitro environment simulating acute APAP overdose.Methods: This study involved the APAP and control groups (ferrous sulfate and chlorpheniramine). The APAP study group contained three subgroups of APAP with different dosage, i.e., 25 g (50 tabs)/37.5 g (75 tabs)/50 g (100 tabs). The positive control group containing ferrous sulfate, i.e., 15 g (50 tabs), has been reported previously to form pharmacobezoars in overdose. The negative control group containing chlorpheniramine, i.e., 200 mg (50 tabs), has not been reported to form pharmacobezoars in previous case studies. Tablets from each study group were placed into a separate pig stomach. Each stomach contained 28 ml USP standard simulated gastric acid. The stomach was placed in a plastic box filled with water maintaining at 37 °C. Each test group was examined for 4 h in the stomach. The primary outcome was the presence of clump formation. Positive clump formation was defined as tablets sticking together and the ability to maintain shape upon dissecting the pig stomach and lifting with fingers. Tablet clumps would then undergo dissolution testing with subsequent analysis of dissolution profiles.Results: Formation of tablets clumps was confirmed in APAP overdose in the in vitro environment. Clumps were noted to be present in the 37.5 g and 50 g APAP groups, while 25 g APAP was unlikely to form clumps. The dissolution profile of clump demonstrated slower release without reaching plateau at 60 min, as compared to corresponding individual tabs of APAP. f1 and f2 analyses showed the dissolution profile of clump was different compared to that of referenced individual tab.Conclusions: APAP clump formation was confirmed in acute overdose of 37.5 g or more. Dissolution tests revealed delayed and steady release of tablet residue from the clumps, which could explain prolonged or delayed toxicity in large APAP overdose.-
dc.subjectin vitro-
dc.subjectmassive overdose-
dc.titleIn vitro study of pharmacobezoar formation in simulated acetaminophen overdose.-
dc.typeJournal Article-
dc.identifier.journaltitleClinical Toxicology-
dc.identifier.affiliationAccident and Emergency Department, Princess Margaret Hospital, Hong Kong, Hong Kong SAR-
dc.identifier.affiliationAustin Toxicology Service, Austin Health, Heidelberg, Victoria, Australiaen
dc.identifier.affiliationDepartment of Emergency Medicine, Austin Health, Heidelberg, Victoria, Australiaen
dc.identifier.affiliationDepartment of Medicine, School of Clinical Sciences at Monash Health, Monash University, Melbourne, Australiaen
dc.identifier.affiliationVictorian Poisons Information Centre, Austin Health, Heidelberg, Victoria, Australiaen
dc.identifier.affiliationDepartment of Medicine and Radiology, Centre for Integrated Critical Care, Melbourne Medical School, University of Melbourne, Melbourne, Australiaen
dc.type.austinJournal Article-, Anselm Y
item.fulltextNo Fulltext-
item.openairetypeJournal Article-
item.openairecristype Poisons Information Centre-
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