therapeutic drug monitoring

(redirected from Lipid solubility)

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 ?
A gasotransmitter typically has high lipid solubility and can penetrate cell membranes without requiring a specific transporter or receptor.
Drug exposure varies according to molecular weight, degree of ionisation, protein binding and lipid solubility.
On the invention of buprenorphine which is more potent than morphine and is agonist--antagonist with lipid solubility about 5 times greater than morphine has been used epidurally for post-operative analgesia.
An aliquot of nhexane was added to each of the reaction vessel to enhance the lipid solubility.
As lipid solubility of sufentanil id=s higher in case of intravenous route this will result into higher penetration of BBB resulting into higher ratio, while in case of epidural route, higher lipid solubility results into larger uptake of it into epidural fat, which ultimately results into decreased potency ratio in comparison to intravenous route.
Self-microemulsifying drug delivery systems are recent and effective approach for the augmentation of oral bioavailability of many poor water soluble drugs provided that the drug should be potent with high lipid solubility.
In an outpatient setting, the high analgesic potency and high lipid solubility of fentanyl allows it to be delivered through a transdermal patch and provide pain relief for patients suffering from chronic pain.
One reason for doxycycline's effectiveness against notoriously recalcitrant bacterial infections such as Borrelia burgdorferi (the spirochete bacterium that causes Lyme disease) and the rickettsial bacteria that cause Rocky Mountain Spotted Fever, anaplasmosis, and ehrlichiosis, is its high lipid solubility, which allows it to attack pathogens that have set up shop in the central nervous system and in the synovial fluid of the joints.
Contrast medium neurotoxicity is thought to be caused by the osmolality, lipid solubility, viscosity, and ionic properties of the contrast agent.
Further experimentation confirmed the involvement of vitamin E's antioxidant function in its repair-promoting benefit, as well as its ability to insert itself into the cell membrane due to its lipid solubility.