Elimination therapeutic drug monitoring

McLachlan AJ, Gross AS, Beal JL, Minns I, and SE Tett (2001). Analytical validation for a series of marker compounds used to assess renal drug elimination processes. Therapeutic Drug Monitoring 23 39 6. 

Renal elimination of unchanged drug accounts for 66% of drug clearance, and the dose should be adjusted for impaired renal function. The role of therapeutic drag monitoring is unknown. It has linear pharmacokinetics and is metabolized in blood by nonhepatic enzymatic hydrolysis. 

Saliva is not an important route of excretion since most of the chemicals present in saliva will eventually reach the gastrointestinal tract to be reabsorbed or eliminated in the feces. The unbound fraction of several therapeutic drugs may diffuse passively from plasma into saliva. This provides a noninvasive means of indirectly monitoring plasma concentrations of drugs like lithium, phenytoin, and theophylline. Metals like lead, cadmium, and mercury are also present in saliva. 

Phase II investigates the compound s efficacy and safety in controlled clinical trials for a specific therapeutic indication. To eliminate as many competing factors as possible, Phase II trials are narrowly controlled. They are characterized as small—several hundred subjects with the indicated disease or symptoms—and are closely monitored. The control may be either a placebo study arm or an active control arm. The endpoint measured may be the clinical outcome of interest or a surrogate. Phase II trials may last for several months or even several years. Early pilot trials to evaluate safety and efficacy are called Phase Ila. Later trials, called Phase lib, are important tests of the compound s efficacy. These trials may constitute the pivotal trials used to establish the drug s safety and efficacy. At least one pivotal trial (most frequently a large, randomized Phase III study) is done. Only about one third of compounds entered into Phase II will begin Phase III studies [61],... 

Diuretics are therapeutic agents used in certain pathological conditions to eliminate bodily fluids. Furosemide and the thiazide diuretics, chlorothiazide, hydrochlorothiazide, and trichlormethiazide are approved for use in dairy cattle for treatment of postparturient edema of the mammary gland and associated structures. The potential misuse of these diuretic drugs in cattle could lead to unacceptable residues in meat or milk destined for human consumption. Therefore, analytical methods sufficiently sensitive to monitor residue concentration levels in foods are valuable in preventing unapproved use of diuretics. 

VINCA ALKALOIDS - VINBLASTINE, VINCRISTINE 1. ANTIBIOTICS-rifampicin 2. ANTICANCER AND IMMUNOMODULATING DRUGS - dexamethasone 3. ANTIDEPRESSANTS-St John s wort 4. ANTI EPILEPTICS -carbamazepine, phenobarbital, phenytoin 1 of plasma concentrations of vinblastine and vincristine, with risk of inadequate therapeutic response. Reports of 1 AUC by 40% and elimination half life by 35%, and t clearance by 63%, in patients with brain tumours taking vincristine, which could lead to dangerously inadequate therapeutic responses Due to induction of CYP3A4-mediated metabolism Monitor for clinical efficacy, and t dose of vinblastine and vincristine as clinically indicated in the latter case, monitor clinically and radiologically for clinical efficacy in patients with brain tumours and t dose to obtain desired response... 

During the hyperthyroid state, other drugs that are metabolized by the liver or eliminated renally may need to be adjusted because metabolism may be increased. Patients using drugs with a narrow therapeutic index such as digoxin, warfarin, and phenytoin should be monitored carefully because dosing adjustments will be necessary as the hyperthyroidism or hypermetabolic state resolves. 

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