Biliary system

ACS Symposium Series American Chemical Society Washington, DC, 1980. 

Equally important is the high affinity binding of the Tc-estradiol analog to the estradiol receptor. The functional group chosen must not interfere with this binding and must be attached to the estradiol molecule at a point which does not interfere with binding to the receptor. The ability of the Tc-compound to 

Attempts to design Tc-radiopharmaceuticals of this type in the past have all failed. The past failures were due, at least in part, to the lack of information on the chemistry of Tc. The availability of new knowledge on the chemistry of Tc (such as that in the chapters by Davison and Deutsch) greatly increases the likelihood that new bifunctional Tc-radiopharmaceuticals will be developed. 

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The biliary system consists of the liver, the gall bladder and its associated drainage ducts which combine with the pancreatic duct to form the common bile duct. Situated in the upper right quadrant of the abdomen this is a highly vascular organ being perfused by... 

Table V contains data for two model substances, p-aminohippurate (PAH) and phenol red. Consideration of the highest values in this table tells you where the major portions of the substances appear. For example, urine and bile show the largest concentrations of PAH and phenol red. Both compounds appear in significant concentrations in the kidney while the values in muscle, brain and cerebrospinal fluid (CSF) are invariably lower than the values seen in plasma. The values in parentheses (Table V) are percent of the administered dose in a given tissue or fluid compartment. They add to the previous information by revealing the overall importance of a particular compartment in the disposition of a substance. For example, while the hepatic concentrations of PAH and phenol red at 4 hrs. are only about 2-fold those of plasma, the large size of the shark liver relative to its body weight, typically about 10%, leads to the appearance of 30-40% of these substances in the liver. The relative handling of these compounds by the urinary and biliary system is obvious from considering the percentage figures. Thus in 24 hours phenol red is about equally distributed in the bile and urine (38 vs 31%) the urinary route is the dominant route of excretion of PAH, i.e., 56 vs 2%.

Some of these triiodinated compounds are orally active, i.e. they are absorbed from the gastrointestinal tract after oral administration and imaging of the biliary system is possible following this route of administration. Examples are iopanoic acid, iophenoxic acid and sodium ipodate. A prerequisite for oral absorption is a balance of relatively hydrophilic and lipophilic moieties in the molecule. Numerous investigations have been performed to establish structure-activity relationships for this class of compounds, e.g. by Archer and Hoppe [70, 71]. Sodium salts are better absorbed than the free acids [72]. 

Clearly we cannot use techniques like these in routine clinical practice to measure the rate of input of drug into the plasma after oral or parenteral administration. Similar arguments apply to measuring drug loss - it is comparatively easy if it s only through the kidney, but very difficult if loss through the biliary system needs to be measured as well. 

Hepatic function abnormal Liver and biliary system disorders 27,769 0.8... 

Excretion, along with metabolism and tissue redistribution, is important in determining both the duration of drug action and the rate of drug elimination. Excretion is a process whereby drugs are transferred from the internal to the external environment, and the principal organs involved in this activity are the kidneys, lungs, biliary system, and intestines. 

The liver secretes about 1 L of bile daily. Bile flow and composition depend on the secretory activity of the hepatic cells that line the biliary canaliculi. As the bile flows through the biliary system of ducts, its composition can be modified in the ductules and ducts by the processes of reabsorption and secretion, especially of electrolytes and water. For example, osmotically active compounds, including bile acids, transported into the bile promote the passive movement of fluid into the duct lumen. In the gallbladder, composition of the bile is modified further through reabsorptive processes. 

Rapidly, completely absorbed. Protein binding greater than 99%. Undergoes minor hepatic metabolism to inactive metabolite. Excreted unchanged in urine and in the feces through the biliary system. Not removed by hemodialysis. Half-life 9 hr. 

Pharmacokinetics Minimal absorption after PO, inhalation, or nasal administration. Absorbed portion excreted in urine or by biliary system. Half-life 80-90 min,... 

Mecfianism of Action An ergotamine derivative, alpha-adrenergic blocker that directly stimulates vascular smooth muscle. May also have antagonist effects on sero-fonin. Therapeutic Effect Peripheral and cerebral vasoconstriction. Pharmacokinetics Slow, incomplete absorption from the gastrointestinal (GI) tract rate of absorption of intranasal route varies. Protein binding greaterthan 90%. Undergoes extensive first-pass metabolism in liver. Metabolized to active metabolite. Eliminated in feces via biliary system. Half-life 7-9 hr. 

Pharmacokinetics Rapidly absorbed after PO administration. Protein binding 98%. Undergoes first-pass metabolism in the liver to active metabolites. Excreted in urine and biliary system. Minimally removed by hemodialysis. Half-life 5-9 hr. 

Well absorbed after IM or topical administration. Transmucosal form absorbed through the buccal mucosa and G1 tract. Protein binding 80%-85%. Metabolized in the liver. Primarily eliminated by biliary system. Half-life 2-4 hr IV 17 hr transdermal 6.6 hr transmucosal. 

Mechanism of Action An antioxidant that prevents oxidation of vitamins A and C, protects fatty acids from aff ack by free radicals, and protects RBCs from hemolysis by oxidizing agents. Therapeutic Effect Prevents and treats vitamin E deficiency. Pharmacokinetics Variably absorbed from the GI tract (requires bile salts, dietary fat, and normal pancreatic function). Primarily concentrated in adipose tissue. Metabolized in the liver. Primarily eliminated by biliary system. 

Pharmacokinetics Readily absorbed from the GI tract (duodenum) after IM or subcutaneous administration. Metabolized in the liver. Excreted in urine eliminated by biliary system. Onset of action with PO form, 6-10 hr with parenteral form, hemorrhage controlled in 3-6 brand PT returns to normal in 12-14 hr. 

Pharmacokinetics Poorly absorbed after IM administration. Protein binding 27%-35%. Metabolized in liver. Excreted in urine. Eliminated in feces via biliary system. Not removed by hemodialysis. Half-life 8.5-9.6 hr (half-life is increased with impaired renal function). 

Mechanism of Action An HMG-CoA reductase inhibitor that interferes with cholesterol biosynthesis by preventing the conversion of HMG-CoA reductase to meva-lonate, a precursor to cholesteroh Therapeutic Effect Lowers serum LDL and VLDL cholesterol and plasma triglyceride levels increases serum HDL concentration. Pharmacokinetics Poorly absorbed from the G1 tract. Protein binding 50%. Metabolized in the liver (minimal active metabolites). Primarily excreted in feces via the biliary system. Not removed by hemodialysis. Half-life 2.7 hr. 

Minimal absorption after oral administration. Hydrolyzed to active form by enzymes of colonic flora. Absorbed drug metabolized in the liver. Eliminated in feces via biliary system. 

Pharmacokinetics Well absorbed from the G1 tract. Metabolized in the liver. Primarily eliminated in feces by biliary system. Half-life 7 days. 

Rapidly, completely absorbed from the GI tract. Protein binding 90%-94%. Metabolized in the liver to active metabolite. Primarily eliminated in feces via biliary system excreted in urine. Not removed by hemodialysis. Half-life 12 hr. 

First-pass metabolism (first-pass effect) The passage of the drug from the portal circulation into hepatocytes and conversion there into metabolites. These metabolites may have a pharmacological profile different from that of the parent drug. They are typically then excreted by the hepatocytes into the biliary system and pass back into the small bowel where enterohepatic recirculation may occur (e.g., benzodiazepines, bupropion, nefazodone, neuroleptics, tricyclic antidepressants). 

The principal objective of drug metabolism is to make a drug available for excretion by urine or bile. The renal and biliary systems can excrete water-soluble molecules, whereas water-insoluble drugs must first be converted to a soluble form before they can be excreted. Drug metabolism, therefore, is principally, but not exclusively, of importance for drugs that are non-polar. Metabolism usually results in inactivation of the drug but there are exceptions, e.g. diazepam is metabolised to an active metabolite desmethyidiazepam, which has a much longer duration of action than the parent compound. 

All thiazides can be administered orally, but there are differences in their metabolism. Chlorothiazide, the parent of the group, is not very lipid-soluble and must be given in relatively large doses. It is the only thiazide available for parenteral administration. Chlorthalidone is slowly absorbed and has a longer duration of action. Although indapamide is excreted primarily by the biliary system, enough of the active form is cleared by the kidney to exert its diuretic effect in the DCT. 

Vinblastine is an alkaloid derived from the periwinkle plant Vinca rosea. Its mechanism of action involves inhibition of tubulin polymerization, which disrupts assembly of microtubules, an important part of the cytoskeleton and the mitotic spindle. This inhibitory effect results in mitotic arrest in metaphase, bringing cell division to a halt, which then leads to cell death. Vinblastine and other vinca alkaloids are metabolized by the liver P450 system, and the majority of the drug is excreted in feces via the biliary system. As such, dose modification is required in the setting of liver dysfunction. The main adverse effects are outlined in Table 54-4, and they include nausea and vomiting, bone marrow suppression, and alopecia. This agent is also a potent vesicant, and care must be taken in its administration. It has clinical activity in the treatment of Hodgkin s... 

Chlortetracycline has, in many respects, a pharmacological profile similar to that of oxytetracycline. Similarly to other tetracyclines, the main excretory routes are through the urinary system, biliary system, and intestine. Its higher biliary excretion rate makes chlortetracycline a better choice than oxytetracycline for liver infections. 

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