Altered Drug Metabolism

Low level activation of MPS Interleukin-I Amyloidosis Hyperplastic liver foci Altered stem cell kinetics Altered drug metabolism Altered response to drugs C Biotechnics For biotechnics (and specifically monoclonal antibodies), factors affecting safety include... 

This approach assumes that fe is known, the change in CL and k are proportional to CLcr, renal disease does not alter drug metabolism, any metabolites are inactive and nontoxic, the drug obeys first-order (linear) kinetic principles, and the drug is adequately described by a one-compartment model. The kinetic parameter/dosage adjustment factor (Q) can be calculated as ... 

Monitoring Monitor whole blood sirolimus concentrations in patients receiving concentration-controlled sirolimus. Monitoring is also necessary in patients likely to have altered drug metabolism, in patients at least 13 years of age who weigh less than 40 kg, in patients with hepatic impairment, and during coadministration of potent CYP3A4 inducers and inhibitors. 

Pharmacogenetics and Altered Drug Metabolism of Chemotherapeutic Agents for Cancer... 

Diet. Diet is shown to affect the absorption, metabolism, and response to many drugs.12,30 Animal and human studies indicated that the total caloric input as well as the percentage of calories obtained from different sources (carbohydrates, proteins, and fats) influence drug pharmacokinetics.17,26 Specific dietary constituents such as cruciferous vegetables and charcoal-broiled beef can also alter drug metabolism.17... 

Current research seeks to further define altered drug metabolizers along ethnic and racial lines. However, since some ethnic groups traditionally underutilize psychiatric services, complete data for these populations may be difficult to obtain. 

The test article is not metabolized by liver microsomes, or hepato-cytes This is indicated by the lack of either metabolite formation or parent disappearance in Studies 1 and 2. Hepatic metabolism is not involved in the metabolic clearance of the compound. There should be no concern with coadministered drugs that can alter drug-metabolizing enzyme activities. 

A number of conditions are indicative of liver disease including (1) jaundice, (2) portal hypertension, (3) abnormal hepatorenal function, (4) altered drug metabolism, (5) nutritional and metabolic abnormalities, (6) disordered hemostasis, and (7) the release of enzymes into various body fluids. 

DDIs Associated With Altered Drug Metabolism... 

DDIs ASSOCIATED WITH ALTERED DRUG METABOLISM... 

Alcoholics are susceptible to drug toxicity, because alcohol induces liver injury and cirrhotic changes that alter drug metabolism. Alcohol causes depletion of glutathione (hepatoprotective) stores, making the person more susceptible to toxicity by drugs (e.g., acetaminophen, statins). 

Freeman DJ, Laupacis A, Keown P, StiUer C, Carruthers G. The effect of agents tiiat alter drug metabolizing enzyme activity on the pharmacokinetics of cyclosporme. AnnR CollPl -sicians Surg Can ( 9S4) 17, 301. 

Santen RJ, Lipton A, Kendall J. Successful medical adrenalectomy widi amino-glutelhimide. Role of altered drug metabolism. JAMA (1974) 230,1661-5. 

The hypersensitive and toxic mechanisms are not mutually exclusive. In some instances, a combined effect might by operating, with antigens being produced only in some subjects because of altered drug metabolism (Klatskin 1974). In addition, a direct toxic mechanism might also alter an immune response, exposing the cell to further injury. 

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