Biliary function

Biliary function Immature Near adult Adult pattern... 

Based on a LOAEL of 5.0 mg/kg BW daily for decreased hepatic biliary function in rats treated with toxaphene in the diet for 8 days and an uncertainty factor of 1000. 

In faulty biliary functioning and general liver sluggishness. Tonic properties particularly applicable to the digestive apparatus. Dose, two tablespoonfuls of the 1 ounce to 1 pint boiling water infusion. 

Liver disease is now recognised as a major complication of type 2 diabetes. Diabetes mellitus can lead to metabolic changes that alter normal hepatic and biliary function and structure. Type 2 diabetes is associated with an increased risk of a range of hepatobiliary diseases, including non-alcoholic fatty liver disease, cirrhosis, acute liver failure, hepatocellular carcinoma and cholelithiasis [22]. 

Disposition in the Body. Well absorbed after oral administration and subject to enterohepatic circulation decreased absorption may occur in subjects with impaired liver and biliary function. Metabolised by hydroxylation to active metabolites. The major metabolite is 25-hydroxycholecalciferol which is formed in the liver. This is further metabolised by la- or 24-hydroxylation in the kidneys. Most of a dose is excreted in the bile and eliminated in the faeces about 25% of a dose is excreted as conjugates. Unchanged cholecalciferol does not appear to be excreted in the urine. 

In chronic-duration exposure studies with animals, an unspecified strain of dogs exposed to ambient air concentrations of 0.05-0.2 mg U/m as uranium hexafluoride for 1 year exhibited increased and persistent bromosulfalein retention, indicative of impaired biliary function, at the 0.2 mg U/m concentration level (Stokinger et al. 1953). 

Plasma bile acids (total bile acids, TBAs) have been recommended as an alternative measurement to plasma bilirubin because TBAs can indicate biliary functionality in terms of the response to food intake. TBA values are dependent upon a number of factors, including stomach emptying gall bladder contraction, where it exists intestinal motility intestinal absorption hepatic uptake and hepatic excretion. The enterohepatic circulation amplifies deficiencies in the hepatic transport system this results in reduced secretion of bile acids into the bile. Studies with dogs have shown that timed postprandial measurements have greater diagnostic value than fasting or random samples (Center et al. 1991 Jensen and Poulsen 1992), but the collection of timed postprandial samples is more difficult. 

Another, though less well-characterised, determinant of oral drug absorption is biliary function, which affects the ability to solubilise and absorb lipophilic drugs. Immature transportation and secretion of biliary salts in the neonatal period may affect drug absorption. 

In phase II of treatment hepatic failure, renal failure, pancytopenia, and rhabdomyolysis were eommon adverse effects. Pharmacokinetic and pharmacodynamic studies show that biliary function can be served as reference parameter to indicate whether patient receive full dose of trabectedin or not. It is also reported that alkaline phosphatase and bilirubin can be served as a high risk indicator in full dose treatment. Phase II clinical trials show that trabectedin has greater efficacy in patient who suffered from breast and ovarian cancer and refractory soft tissue sarcoma. A search in Pubmed shows that there are several studies reporting the results of clinical trials (phase I, II and III) on the efficacy of trabectedin against ovarian cancer. Ferrandina et al. [38] performed retrospective, multicenter study to determine the potential efficacy of trabectedin as single agent in 98 patients (67 platinum sensitive, and 31 platinum refractory/resistant) who suffered from heavily relapsed ovarian cancer. They found that trabectedin treatment can prolong the survival of patients (18 month for treatment vs. 14 month for SD). They also found that hepatotoxicity and rare cardiotoxicity were the most important adverse effects of trabectedin treatment [38]. 

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