therapeutic drug monitoring

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therapeutic drug monitoring

Clinical pharmacology The regular measurement of serum levels of drugs requiring close 'titration' of doses in order to ensure that there are sufficient levels in the blood to be therapeutically effective, while avoiding potentially toxic excess; drug concentration in vivo is a function of multiple factors Common TDM drugs Carbamazepine, digoxin, gentamycin, procainamide, phenobarbital, phenytoin, theophylline, tobramycin, valproic acid, vancomycin
Therapeutic drug levels in vivo–factors involved
Patient compliance  Ingestion of drug in the doses prescribed
Bioavailability Access to circulation, interaction with cognate receptor(s); ionized and 'free', or bound to a carrier molecule, often albumin
Pharmacokinetics Drug equilibrium requires 4-6 half-lives of drug clearance (a period of time for1/2 of the drug to 'clear', either through metabolism or excretion, multiplied by 4-6); the drug is affected by
Interaction with foods or other drugs at the site of absorption, eg tetracycline binding to cations or chelation with binding resins, eg bile acid-binding cholestyramine that also sequesters warfarin, thyroxine and digitoxin or interactions of various drugs with each other, eg digitalis with quinidine resulting in a 3-fold ↓ in digitalis clearance
Absorption may be changed by GI hypermotility or large molecule size
Lipid solubility, which affects the volume of distribution; highly lipid-soluble substances have high affinity for adipose tissue and a low tendency to remain in the vascular compartment, see Volume of distribution.
Biotransformation, with 'first pass' elimination by hepatic metabolism, in which polar groups are introduced into relatively insoluble molecules by oxidation, reduction or hydrolysis; for elimination, lipid-soluble drugs require the 'solubility' steps of glucuronidation or sulfatation in the liver; water-soluble molecules are eliminated directly via the kidneys, weak acidic drugs are eliminated by active tubular secretion that may be altered by therapy with methotrexate, penicillin, probenecid, salicylates, phenylbutazone and thiazide diuretics
First order kinetics Drug elimination is proportional to its concentration
Zero order kinetics Drug elimination is independent of the drug's concentration
Physiological factors
Age Lower doses are required in both infants and the elderly, in the former because the metabolic machinery is not fully operational, in the latter because the machinery is decaying, with ↓ cardiac and renal function, enzyme activity, density of receptors on the cell surfaces and ↓ albumin, the major drug transporting molecule
Enzyme induction, which is involved in a drug's metabolism may reduce the drug's activity; enzyme-inducing drugs include barbiturates, carbamazepine, glutethimide, phenytoin, primidone, rifampicin
Enzyme inhibition, which is involved in drug metabolism, resulting in ↑ drug activity, prolonging the action of various drugs, including chloramphenicol, cimetidine, disulfiram (Antabuse), isoniazid, methyldopa, metronidazole, phenylbutazone and sulfonamides
Genetic factors play an as yet poorly defined role in therapeutic drug monitoring, as is the case of the poor ability of some racial groups to acetylate drugs
Concomitant disease, ie whether there are underlying conditions that may affect drug distribution or metabolism, eg renal disease with ↓ clearance and ↑ drug levels, or hepatic disease, in which there is ↓ albumin production and ↓ enzyme activity resulting in a functional ↑ in drug levels, due to ↓ availability of drug-carrying proteins

ther·a·peu·tic drug mon·i·tor·ing

(TDM) (thār'ă-pyū'tik drŭg mon'i-tŏr-ing)
Clinical measurement of the effects of a drug in a specific patient rather than reliance on normative ranges (e.g., some old people need a lower dosage than their weight might suggest). Such procedures verify that therapy is as accurate as possible.
References in periodicals archive ?
It will enable researchers to identify the genetic factors that determine why drugs work well for some patients, but not for others.
However, because we know that genetically influenced traits such as low self control affect delinquent behaviour, and delinquents, particularly violent ones, tend to associate with antisocial peers, I had reasons to suspect that genetic factors could influence the odds of someone becoming a victim of crime, and these formed the basis of our study," he added.
Proposals might consider mechanistic factors such as 1) regulation of ion transport, cytoskeleton effects, neurotransmitter levels, and enzyme activities following oral exposure; 2) differences between the pharmacokinetics of water, food, and inhalation exposures; 3) variations in bioavailability and metabolism; and 4) other factors that affect human susceptibility, such as genetic factors, diet, age, sex, and predisposing health conditions.
The picture is incomplete, Nussenzweig says, because autoimmune reactions probably require other genetic factors.
But the genetic factors identified so far explain only a small percent of all the cases in the general population," Nature magazine quoted Zheng, an Ingram Professor of Cancer Research, professor of Medicine and the director of the Vanderbilt Epidemiology Center, as saying.
These results indicate that obesity involves more than one gene, that genetic factors more often affect younger women, and that variants near the OB gene also play a role in the emotional makeup of obese women," contends study director David E.
Its mission is to facilitate biomedical research that is pursuing advances in identifying human genetic factors affecting the skin and formulating products and therapies to target issues specific to the individual customer, both for prevention and treatment.
Investigators will explore multiple gene interactions and genetic factors working in concert with environmental factors such as nutrition and exposures to chemicals.
Smithies believes this information will prove helpful in ferreting out the genetic factors in human essential hypertension.
Perlegen is currently using these SNPs to perform whole genome association studies to determine the genetic factors responsible for complex traits such as disease and differential drug response.
Other genetic factors underlying coronary disease are generally less common than this mutation, Hayden asserts.
Identification of new genetic factors associated with AD will lead to a better understanding of the molecular mechanisms underlying the disease and provide a basis for new approaches to diagnosis, treatment, and prevention.