zero order kinetics

zero order kinetics

a state at which the rate of an enzyme reaction is independent of the concentration of the substrate.

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
References in periodicals archive ?
F06 seemed to follow zero order kinetics with super case II mechanism of drug release.
The order of drug release from the matrix systems was described by using zero order kinetics or first orders kinetics.
This fact shows that the reactions exhibit 1 to zero order kinetics with respect to all diols indicating Michaelis-Menten kinetics.
To study the kinetics of liner wear it was found that a zero order kinetics model could well be used to describe the data.
4]-N from the water column appeared to be best represented by zero order kinetics, as the regression equation was linear to 0 mg [L.
The mechanism for coalescence was related to the loss in weight of dispersing liquid during an initial zero order kinetics stage.
This new CDT(TM) amino acid patent, in conjunction with the CDT(TM) salt patent and CDT(TM) dual polymer patent, combine to create a range of modified oral drug delivery systems which address the most challenging hurdles of oral drug delivery, including zero order kinetics, poorly soluble active ingredients and ingredients difficult to tablet.
The order of drug release from matrix systems was described by using zero order kinetics or first orders kinetics.
This new CDT(TM) amino acid technology, in conjunction with the CDT(TM) salt patent and CDT(TM) dual polymer patent, combine to create a range of modified oral drug delivery systems -- which address the most challenging hurdles of oral drug delivery, including zero order kinetics, poorly soluble active ingredients and ingredients difficult to tablet.
Our CDTTM drug delivery platforms have been shown to be fast to formulate, simple to develop and scale-up to commercial batches and, most importantly, we can provide high value controlled delivery formulations with first or zero order kinetics at approximately the same cost of manufacture as immediate release products.
Nutraceutix is currently addressing some of the most challenging hurdles of oral drug delivery: difficult to tablet ingredients, zero order kinetics (linear release), and poorly soluble active ingredients.