Liver and elimination

Amsacrine (m-AMSA) is a synthetic aminoacri-dine which intercalates into DNA and inhibits DNA topoisomerase II. m-AMSA is not cross-resistant to anthracyclines and has been particularly active in acute non-lymphocytic leukemia. Amsacrine is administred by intravenous infusion. It is metabolized in the liver and eliminated in the bile with an elimination half-life of 6-9 hours. Its major toxicity is bone marrow depression. Gastrointestinal disturbances are frequent. Neurotoxicity and cardiotoxic-ity may occur. 

The most important processes assessed in pharmacokinetic studies are absorption (uptake of a drug from the digestive tract), distribution (compart-mentalization in the body), metabolism (conversion or breakdown, especially in the liver) and elimination (excretion), summarized by the abbreviation ADME. 

Oral bioavailability of telithromycin is 57%, and tissue and intracellular penetration is generally good. Telithromycin is metabolized in the liver and eliminated by a combination of biliary and urinary routes of excretion. It is administered as a once-daily dose of 800 mg, which results in peak serum concentrations of approximately 2 mcg/mL. Telithromycin is indicated... 

Meanwhile, in the process of clearing heat from the Liver and eliminating dampness, it is also important to strengthen the Yin and promote blood circulation, spread the Liver-Qi and protect the Stomach, as all of them can be disturbed by intense heat and by those very cold herbs. 

Imatinib is administered orally and is well absorbed it is highly protein-bound in plasma. The drug is metabolized in the liver, and elimination of metabolites occurs mainly in feces via biliary excretion. This agent is approved for use as first-line therapy in chronic phase CML, in blast crisis, and as second-line therapy for chronic phase CML that has progressed on prior interferon- therapy. Imatinib is effective also for treatment of gastrointestinal stromal tumors expressing the c-kit tyrosine kinase. Dosage and toxicities are listed in Table 55-6. 

Urea A waste product of the metabolism of proteins that is formed by the liver and eliminated from the body through the kidneys as urine. 

Studies show that the main sites of uranium deposition are the renal cortex and the liver (8). Uranium is also stored in bones deposition in soft tissues is almost negligible. Uranium (VT) is deposited mostly in the kidneys and eliminated with the urine whereas, tetravalent uranium is preferentially deposited in the liver and eliminated in the feces. The elimination of uranium absorbed into the blood occurs via the kidneys in urine, and most, 84%, of it is cleared within 4 to 24 hours (8). 

Pharmacokinetics. Amiodarone is effective given orally its enormous apparent distribution volume (701/kg) indicates that little remains in the blood. It is stored in fat and many other tissues and the t) of 54 days after multiple dosing signifies slow release from these sites (and slow accumulation to steady state means that a loading dose is necessary, see Table 24.1). The drug is metabolised in the liver and eliminated through the biliary and intestinal tracts. 

By inhalation the nicotine in tobacco smoke reaches the brain in seven seconds. Brain levels thus rise rapidly, but then they fall rapidly because nicotine is quickly distributed to other sites of action. Nicotine is metabolized primarily in the liver and eliminated mostly in urine. 

Pharmacokinetic PB 96% Well absorbed in GI tract, metabolized in liver, and eliminated in urine and feces... 

Ropivacaine is an amide-type LA, a vasoconstrictor at less than 1% and a vasodilator at more than 1%. The fact that it is the pure S-enantiomer reduces its toxicity. Like phenol, it is metabolized by the liver and eliminated by the kidneys. When administered by dermal injection, it has a rapid onset of action (less than a minute) and the duration of action is longer than or equal to that of bupivacaine. Combining it with adrenaline does not prolong its duration of action, and a concentration of 0.75% provides longer anesthesia than a concentration of 1%. Neurological and cardiovascular tolerance to ropivacaine is much better than to bupivacaine. What is more, there is a considerable difference between the neurotoxic and cardiotoxic doses. The toxicity of ropivacaine is intermediate between that of lidocaine and bupivacaine. Direct intravascular injection of ropivacaine is still dangerous, however. 

As clearance decreases, because of a disease process, half-life would be expected to increase. However, this reciprocal relationship is exact only when the disease does not change the volume of distribution. For example, as Klotz and coworkers have shown, the increase in half-life of diazepam with age does not result from a decrease in clearance but rather results from an increase in volume as the patient ages (12). Clearance, a measure of the body s ability to eliminate the drug, does not significantly decrease with age for diazepam. However, when volume increases, less drug is in the blood flowing to the liver, and elimination can occur only for those molecules that... 

No experimental data regrading methods for reducing the ammonia body burden were located. In healthy people, ammonia is efficiently metabolized via the urea cycle, primarily in the liver, and eliminated in the urine and feces (Fiirst et al. 1969 Richards et al. 1975). 

Atropine is metabolized by the liver and eliminated through the urine. Secondary routes of elimination include excretion through the bile and expired air. 

Ophthalmic corticosteroids are metabolized in surrounding tissues. As a result, the duration of action is longer, because they are eliminated more slowly than systemic steroids, which are metabolized in the liver and eliminated through the bile or urine. 

ABSORPTION, FATE, AND EXCRETION Praziquantel is readily absorbed after oral administration, and maximal levels in human plasma occur in 1-2 hours. Extensive first-pass metabolism to inactive hydroxylated and conjugated products limits drug bioavailability and results in plasma concentrations of metabolites at least 100-fold higher than that of praziquantel. The drug is 80% bound to plasma proteins. Its plasma is 1-3 hours but may be prolonged in patients with severe liver disease, including those with hepatosplenic schistosomiasis. About 70% of an oral dose of praziquantel is recovered as metabolites in the urine within 24 hours most of the remainder is metabolized in the liver and eliminated in the bUe. 

Studies of the metabolism of vitamin E were triggered by the observations of Alaupovic and coworkers [126, 127]. When " [Cj-D-a-tocopherol-5-methyl was administered to rats or pigs and attempts were made to detect metabolic derivatives, two compounds were separated by chromatography. One of the compounds is " [C]-D-a-tocopherol quinone the other is either a dimer or a trimer of a-tocopherol. The dimer and trimer are terminal oxidation products of a-tocopherol and are excreted in the bile. a-Tocopherol quinone can be converted to a-hydroquinone. a-Tocopherol hydroquinone may be esterified in liver and eliminated in the feces after concentration in the bile and excretion in the intestine, or it may be oxidized in the kidney to a-tocopheronic acid, which may be converted into an a-tocopheronolactone conjugate, which is excreted in the urine. In conclusion, vitamin E is excreted as such in the urine or the bile after conversion to a dimer or a trimer, in the form of a conjugated hydroxy-quinone or tocopheronic acid (see Fig. 4-43). 

---