Hepatobiliary

Technetium-99m teboroxime is a myocardial imaging agent and is excreted primarily by the hepatobiliary system. It is rapidly taken up by the myocardium and mosdy washes out within 30 minutes. Imaging protocols are performed immediately after injection. The product is a lyopbili ed mixture of boronic acid, dioxine, and other excipients, and the agent is formed with a beating step. 

Technetium-99m disofenin is used for hepatobiliary imaging. Disofenin (2,6-diisopropylphenylcarbamoyhnethyliminodiacetic acid) is the active ingredient. Product formation is accompHshed by addition of up to 3.7 GBq (100 mCi) of Tc pertechnetate. 

Technetium-99m mebrofenin is an iminodiacetic acid derivative used as a hepatobiliary agent. The kit is suppHed as a single vial containing lyopbilized mebrofenin. The reconstituted kit has 18-hour usage, owing to the preservative, propylparaben. 

Shitara Y, Sato H, Sugiyama Y (2005) Evaluation of drug-drug interactions in the hepatobiliary and renal transport of drugs. Annu Rev Pharmacol Toxicol 45 689-723... 

Liver Gadolinium EOB DTPA Primovist MRI product, not approved for CT phase I, II clinical trials Uptake into hepatocytes Schmitz SA et al (1997) Detection of focal liver lesions CT of the hepatobiliary system with gadoxetic acid disodium, or Gd-EOB-DTPA. Radiology 2002 399-405... 

Dutartre H, Bussetta C, Boretto J, Canard B (2006) General catalytic deficiency of hepatitis C virus RNA polymerase with an S282T mutation and mutually exclusive resistance towards 2 -modified nucleotide analogues. Antimicrob Agents Chemother 50 4161 169 Elferink RO, Groen AK (2002) Genetic defects in hepatobiliary transport. Biochim Biophys Acta... 

Pauli-Magnus C, Meier PJ (2006) Hepatobiliary transporters and drag-induced cholestasis. Hepatology 44 778-787... 

Batsakis, G. Sodeman, T. A. and Deegan, M. J. Enzymatic evaluation of hepatobiliary disease. Laboratory Med. 

Hepatobiliary disease occurs due to bile duct obstruction from abnormal bile composition and flow. Hepatomegaly, splenomegaly, and cholecystitis may be present. Hepatic steatosis may also be present due to effects of malnutrition. The progression from cholestasis (impaired bile flow) to portal fibrosis and to focal and multilobar cirrhosis, esophageal varices, and portal hypertension takes several years. Many patients are compensated and asymptomatic but maybe susceptible to acute decompensation in the event of extrinsic hepatic insult from viruses, medications, or other factors.7... 

Serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, y-glutamyl transferase, and bilirubin may be elevated in patients with hepatobiliary disease. 

Daunorubicin is an anthracycline that is sometimes referred to as an antitumor antibiotic. Daunorubicin inserts between base pairs of DNA to cause structural changes in DNA however, the primary mechanism of cytotoxicity is the inhibition of topoisomerase II. The pharmacokinetics are best described by a two-compartment model, with a terminal half-life of about 20 hours. The predominant route of elimination of daunorubicin and hydroxylated metabolites is hepatobiliary... 

Fig. 5. Chelating agents used to formulate "mTc-hepatobiliary imaging agents A) Mebrofenin R2.4.6 =CH3, R3 = Br, R5=H and Disofenin R2 6 = CH(CH3)2 R3 5 = H B) N-pyridoxyl-5-methyltryptophan (PMT)...

Muller, M. and P. L. Jansen. Molecular aspects of hepatobiliary transport. Am. J. Physiol. 1997, 272, G1285-G1303. 

Smit, J. W., et al. Contribution of the murine mdrla P-glycoprotein to hepatobiliary and intestinal elimination of cationic drugs as measured in mice with an mdrla gene disruption. Hepatology 1998, 27, 1056-1063. 

Hooiveld, G. J., et al. Function and regulation of ATP-binding cassette transport proteins involved in hepatobiliary transport. Eur. J. Pharm. Sci. 2000, 32, 13-30. 

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. 

If the unbound drug concentrations in plasma are higher than their K values on the transporters, then transporter function may be significantly affected [106], Following a pharmacokinetic analysis of the effect of probenecid on the hepatobiliary excretion of methotrexate, it has been shown the extent of an in vivo drug-drug interaction can be quantitatively predicted from the kinetic parameters for transport across the sinusoidal and bile canalicular membranes determined in vitro [107]. 

Oude Elferink, R. P., Meijer, D. K., Kuipers, F., Jansen, P. L., Groen, A. K., Groothuis, G. M., Hepatobiliary secretion of organic compounds molecular mechanisms of membrane transport, Biochim. Biophys. Acta 1995, 1241, 215-268. 

Pagels, P., Starke, D., Kramer, W., Hepatobiliary transport of bile add amino add, bile add peptide, and bile acid oligonucleotide conjugates in rats, Hepatology 1999, 30, 1257-1268. 

B., Meijer, D. K., Hepatobiliary and intestinal clearance of amphiphilic cationic drugs in mice in which both mdrla and mdrlb genes have been disrupted, Br. J. Pharmacol. 1998, 124, 416-424. 

Oude Eleerink, R., Groen, A. K., Genetic defects in hepatobiliary transport, Biochim. Biophys. Acta 2002, 1586, 129-145. 

Kato, Y., Akhteruzzaman, S., Hisaka, A., Sugiyama, Y., Hepatobiliary transport governs overall elimination of peptidic endothelin antagonists in rats,/. Pharmacol. Exp. Ther. 1999, 288, 568-574. 

Dervenis C, Smailis D, Hatzitheoklitos E Bacterial translocation and its prevention in acute pancreatitis. J Hepatobiliary Pancreat Suig 2003 10 415 118. 

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