Physiologically based pharmacokinetic modeling of hydrogen cyanide in humans following the oral administration of potassium cyanide and cyanogenic glycosides from food

Abstract

Cyanogenic glycosides (CGs) are commonly found in some edible plants and seeds. After ingestion, CGs can release toxic hydrogen cyanide (HCN) in humans. At present, unfortunately, there is no tool capable of predicting the cyanide concentration in human blood and organs following oral administration of CG-containing food. The aim of this study was to develop a physiologically based pharmacokinetic (PBPK) model of cyanide following the ingestion of CG-containing food in humans. To develop this model, pharmacokinetic data concerning cyanide concentration levels in humans exposed to potassium cyanide (KCN) and CG-containing foods (persipan paste, linseed, cassava, and bitter apricot kernels) were obtained from published data. This study created a model structure consisting of four organ compartments including the lungs, kidneys, liver, and slowly perfused tissues by employing Berkeley Madonna software to extract three unknown parameters including the maximum velocity of rhodanese, the absorption rate constant, and the bioavailability for oral administration of KCN and the four CG-containing foods (equivalent a 6.8 mg dose of cyanide). The model was then validated by comparing the simulated results for the concentration-time courses of cyanide levels in venous blood with data from two clinical studies covering the oral administration of KCN and linseed at three other doses.