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
McGraw-Hill Concise Dictionary of Modern Medicine. © 2002 by The McGraw-Hill Companies, Inc.

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.
Medical Dictionary for the Health Professions and Nursing © Farlex 2012
References in periodicals archive ?
3 and reaction followed pseudo first order kinetics with respect to ascorbic acid as shown in Fig.
The results showed that the correlation coefficients, R 2 obtained for both adsorbents for pseudo first order kinetics model (0.8761 and 0.876) were lower than their corresponding pseudo second order kinetics model (R 2 = 0.9626, 0.9906) and the experimental qe (177.
Some of the reported studies [18-20] on oil shale modelling have employed first order kinetics as indicated in Equation (1):
The isomerisation reaction follows a first order kinetics as in the thermally induced isomerisation of 9c fatty acids in triolein [13].
Consequently, our data further confirm that exercise transitions to steady state V[O.sub.2] do not obey linear first order kinetics as was assumed by earlier research (1, 4, 6, 9, 10, 13, 25, 31).
where [phi] is the Thiele modulus, which for first order kinetics is
Small molecule degradation, involving one kind of molecule proceeds according to first order kinetics and the degradation rate at standard storage conditions can be estimated with good accuracy by the Arrhenius equation.
First order kinetics: In (1 - F) = [k.sub.1]t (2) where F represents the fraction of drug released in time t and [k.sub.1] is the first-order release constant.
The plots of the above models revealed that adsorption of cyanide follows second order adsorption kinetics showing [R.sup.2] >0.99 as compared to the first order kinetics having [R.sup.2] <0.1.
To describe the diffusional transport of the drug the following premises were used: at the surface of the dosage the drug concentration is constant; the release of the drug follows a first order kinetics (the release rate is proportional to its concentration); diffusion is isotropic (it does not depend on the spatial direction); the convective process is insignificant, thus it can be neglected; the release of the drug from the cylinders occurs only in axial direction (Siepmann et al., 2006).
In this paper, four experiments of first order kinetics were compared for accuracy and precision of results, with the goal of identifying the "best" verification experiment.

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