Hepatobiliary excretion hepatocyte

MDCK II cells (Fig. 12.3) [93], Kinetic analysis revealed that the Km value for transcellular transport (24 pM) was similar to the Km for OATP2 (34 pM) [93], Moreover, the efflux across the bile canalicular membrane was not saturated under these experimental conditions. These in vitro observations are consistent with in vivo experimental results in rats which showed that the rate-determining process for the biliary excretion of pravastatin is uptake across the sinusoidal membrane. By normalizing the expression level between the double transfectant and human hepatocytes, it might be possible to predict in vivo hepatobiliary excretion. 

It has been suggested that multidrug resistance proteins (MRPs) play an important role in the transport and detoxification of a wide range of endogenous compounds and xenobiotics. They are predominantly expressed at the apical membrane of the small intestine, proximal tubules of the kidney and canalicular membrane of hepatocytes involved in intestinal, renal and hepatobiliary excretion of compounds. 

Hepatic extraction efficiency decreases with increasing serum bilirubin levels. With impaired hepatocyte function, high plasma concentrations (>8 mg/100 ml) may inhibit uptake of Tc-IDA complexes. As hepatobiliary excretion decreases, renal accumulation of certain " Tc-IDA complexes is observed (Fink-Bennett 1995). 

LeeJK, Marion T, AbeK, LimC, PollackGM, Brouwer KL. Hepatobiliary disposition of troglitazone and metabolites in rat and human sandwich-cultured hepatocytes Use of Monte Carlo simulations to assess the impact of changes in biliary excretion on troglitazone sulfate accumulation. f Pharmacol Exp Ther. 2010 332(l) 26-34. 

Among the many ligands that have been evaluated, " Tc-mebrofenin has shown the best in vivo characteristics, namely high hepatocyte extraction (98%) and a fast clearance (Ti,2= 17 min), a rapid hepatobiliary-to-bowel transit time, and low urinary excretion. Tc-mebrofenin provides excellent visualization of the common bile duct and the gallbladder at serum bilirubin levels as high as 30 mg/100 ml (Fink-Beimett 1995 Krishnamurthy and Turner 1990). 

Hepatobiliary Tc radiopharmaceuticals are expected to demonstrate a highly specific liver uptake and biliary excretion. Other organs such as the kidneys should not interfere with the imaging of the liver and the biliary tract. The agents should show a rapid hepatocyte transit, clearing the radioactivity in the hepatocytes quickly into the... 

A variety of liver contrast agents have been developed for contrast-enhanced MR imaging of the liver, which are designed to overcome the limitations of extracellular low molecular gadolinium chelates. The two main classes of liver-specific contrast agents are the superparamagnetic iron oxide (SPIO) with uptake via the reticuloendothelial system (RES) mainly into the liver and spleen, and the hepatobiliary contrast agents with uptake into hepatocytes followed by variable biliary excretion. 

---