Pharmacokinetics of biliary excretion of N-nitrosodimethylamine in rats fed diets containing levels of protein.

Albino Wistar rats (Rattus norvegius) fed semi-purified diets containing 3.5%, 8%, 27%, and 64% casein, respectively, as the protein source, were poisoned with an intraperitoneal dose of 20mg N-nitrosodimethylamine (NDMA)/kg, following cannulation of the bile duct, in vitro, under urethane anaesthesia. Bile exudates was collected at designated time intervals and analysed for unchanged NDMA using thin layer chromatography and gas liquid chromatography methods. Rats on 64% high protein diet (HPD) were the highest excretors of NDMA, followed by rats on the 3.5% kwashiorkorigenic diet (KWD), 8% low protein diet (LPD) and 27% normal protein diet (NDP) as the least excretors, in that order. The corresponding values for culmulative excretions of NDMA were 4.38%, 2.74%, 2.96% and 4.11%, and for elimination rate contents they were 54.05Kh(-1), 23.01Kh(-1), 23.76Kh(-1) and 48.88Kh(-1), while the respective elimination half-life values were 0.013h, 0.031h, 0.029h and 0.014h. The toxicological and pharmacological implication of the pharmacokinetic findings are discussed.