Drug metabolism renal

Drug metabolism, renal tubular secretion, and biliary secretion are usually mediated by metabolizing enzymes or transporter proteins. These protein systems usually possess good substrate selectivity with finite capacities, which are described by the Michaelis-Menten equation,... 

The renal clearance can be under estimated in the case of renal drug metabolism. The total drug clearance depends on bioavailability. Therefore, the most reliable estimate for the fraction eliminated by the renal route (fren) is given by the normal clearance (Clnorm) and drug clearance in case of acute and/ or chronic renal failure (Clfail), or from half-lives (Tl/2norm) and (Tl/2fail). 

Several studies have evaluated dietary supplements such as isoflavones, which are found in soy products and red clover. A well-controlled trial in more than 400 postmenopausal women evaluating a specific isoflavone, ipriflavone, found no benefits on bone mineral density or fracture rates after 3 years.47 Nevertheless, because these therapies are available without prescription and are not regulated by the FDA, patients may choose to self-medicate with isoflavones. Lymphocytopenia appeared in several patients treated with ipriflavone in clinical trials. Additionally, ipriflavone should be used with caution in immunocompromised patients or those with renal disease. It may inhibit CYP1A2 and CYP2C9 and may interact with drugs metabolized by those pathways, such as warfarin. 

Pharmacodynamics Duration 1-4 weeks Absorption IM slow Time to peak serum levels 12-24 hours Duration 15-24 hours Absorption IM slow Distribution Poor blood-brain barrier penetration, enters breast milk Metabolism =30% hepatic inactivation Protein binding 65% Time to peak serum levels 1-4 hours Excretion Urine (60-90% as unchanged drug) Clearance Renal... 

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 ... 

Extrapolation of the result to the patient population (especially children or patients with hepatic or renal diseases affecting drug metabolism)... 

Caution Recommended doses do not apply for adult patients with body weight less than 50 kg. Recommended doses do not apply to patients with renal or hepatic insufficiency or other conditions affecting drug metabolism and kinetics. Starting doses should be lower for elderly patients. 

Renal/Hepatic function impairment The drug is metabolized in liver and excreted by the kidney administer with caution to patients with such impairment. Extensive liver disease predisposes to greater side effects and may be the result of decreased drug metabolism. 

The conversion of 6-deoxy penciclovir to penciclovir is catalyzed by aldehyde oxidase. Interactions with other drugs metabolized by this enzyme could occur. Concurrent use with probenecid or other drugs significantly eliminated by active renal tubular secretion may result in increased plasma concentrations of penciclovir. Drug/Food interactions When famciclovir was administered with food, penciclovir Cmax decreased approximately 50%. Because the systemic availability of penciclovir (AUC) was not altered, it appears that famciclovir may be taken without regard to meals. 

Vamvakas S, Muller DA, Dekant W, et al. 1988b. DNA-binding of sulfur-containing metabolites from S-(pentachlorobutadienyl)-L-cysteine in bacteria and isolated renal tubular cells. Drug Metabolic Interact 6 349-358. 

However, the physiology of ageing includes poorer gastrointestinal absorption, somewhat reduced hepatic drug metabolism, and, commonly, a loss of lean body mass. While all of these have been documented, none is of as great a significance as the loss of renal excretory function which is invariably present in old age. 

In the oral cavity, drug metabolism occurs in mucosal epithelial cells, microorganisms, and enzymes in the saliva metabolism also takes place in renal and hepatic tissue once the drug is swallowed. Although biotransformation of agents in the oral cavity is potentially an important aspect of reducing effective drug concentra-... 

Small molecules are eliminated from the body largely by means of drug metabolism enzymes in the liver and other tissues and by urinary excretion. Large molecules are also eliminated by renal and hepatic mechanisms. Proteins that are less than 40 to 50 kDa are cleared by renal filtration with little or no tubular reabsorption. Larger proteins are less likely to be filtered but may be subject to phagocytosis in hepa-tocytes and Kupfer cells in the liver. Protein biotransformation—denaturation, proteolysis, and oxidative metabolism—is also important. 

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. 

Inhibits hepatic microsomal drug-metabolizing enzymes. (Ranitidine, famotidine, and nizatidine do not.) May inhibit the renal tubular secretion of weak bases. 

Unlike renal function, hepatic maturation is generally believed to be a two-stage process with the major development completed at 4 weeks postpartum and tlie second stage completed by about 10 weeks of age. In sheep, for example, tlie activity of a number of hepatic drug-metabolizing enzymes was found to be relatively low in animals aged up to 6 months compared with adult individuals... 

Runge-Morris, M., Feng, Y, Zangar, R.C. Novak, R.F. (1996) Effects of hydrazine, phenelzine, and hydralazine treatment on rat hepatic and renal drug-metabolizing enzyme expression. DrugMetab. Disp., 24, 734-737... 

Pichette V, Leblond FA. Drug metabolism in chronic renal failure. Curr Drug Metab. 2003 4 91-103. 

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