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 ?
According to the therapeutic drug monitoring market report, one driver in the market is increasing demand for personalized medicine.
Therapeutic drug monitoring is utilised by physicians to monitor an individual's response to biologic drugs, as they vary greatly from patient to patient.
Advances in chromatographic techniques for therapeutic drug monitoring.
One of the biggest salvage research questions today is where would the therapeutic drug monitoring (TDM) lest be most useful in the salvage paradigm?
Considering both the data published in the RE-LY substudy and the information reviewed in the British Medical Journal investigative report, dose optimization and therapeutic drug monitoring would be beneficial for many patients.
His interests include quality use of medicines, pharmacokinetic drug-drug interactions, adverse drug reactions, therapeutic drug monitoring, and application of clinical pharmacology principles to endocrine research and practice.
of Texas-Houston) explains possible sources of errors in therapeutic drug monitoring and testing for drugs of abuse, and how to resolve such errors and identify discordant specimens.
The Dimension Vista Intelligent Lab System offers a test menu of more than 140 assays and test panels for anemia, cardiac disease, thyroid disorder, therapeutic drug monitoring, protein testing, fertility, drugs-of-abuse, and routine and specialty chemistry testing--all on one system and from a single patient sample.
The 13 chapters on therapeutic drug monitoring discuss such issues as monitoring free drug concentration; analytical techniques for measuring concentrations of therapeutic drugs in biological fluids; the pre-analytical phase of drug testing; the effect of hemolysis, high bilirubin, lipemia, paraproteins, and system factors on therapeutic drug monitoring; interferences with measurement of anticonvulsants; pitfalls in measuring antidepressant drugs; immunosuppressive drugs; therapeutic monitoring in HIV/AIDS; pharmacogenomics and personalized medicine; interference of heterophilic and other antibodies in measurement of therapeutic drugs by immunoassays; and drug-herb and drug-food interactions and their impact on drug monitoring.
Therapeutic drug monitoring (TDM) [2] is one of the most complex laboratory testing processes in modern laboratory medicine practice.

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