Elimination, of drugs

Electrospray Ionization Mass Spectrometry (ESI-MS) Elimination Half-life Elimination of Drugs EM-800... 

What are the principal routes for the elimination of drugs from the body ... 

Kusuhara, H. and Y. Sugiyama. Role of transporters in the tissue-selective distribution and elimination of drugs transporters in the liver, small intestine, brain and kidney. J. Control. Release 2002, 78, 43-54. 

Dresser MJ, Leabman MK, Giacomini KM. Transporters involved in the elimination of drugs in the kidney organic anion transporters and organic cation transporters. J Pharm Sci 2001 90(4) 397-421. 

The answers are 31-b, 32-a, 33-d (Katzung, pp 4—7.) The absorption, distribution, and elimination of drugs require that they cross various cellular membranes The descriptions that are given in the question define the various transport mechanisms. The most common method by which ionic compounds of low molecular weight (100 to 200) enter cells is via membrane channels. The degree to which such filtration occurs varies from cell type to cell type because their pore sizes differ. 

The answer is b. (Katzungr pp 806—807J Rifampin induces cytochrome P450 enzymes, which causes a significant increase in elimination of drugs, such as oral contraceptives, anticoagulants, ketoconazole, cyclosporine, and chloramphenicol. It also promotes urinary excretion of methadone, which may precipitate withdrawal. 

Elimination Rate Constant, (Kd), is a crucial pharmacokinetic parameter which measures the rate of elimination of drugs from the body. Kd is specific for a given drug, and has the units of time"1. When the Kd is greater, the drug is eliminated rapidly. It is calculated from the slope of the terminal portion of the log plasma concentration versus time profile. From the terminal portion of the plasma concentration versus time profile, Kd is calculated as,... 

Clearance refers to the elimination of drug from the body. It is defined as the volume of blood which is completely cleared of drug per unit time. The drug can be eliminated via excretion through kidneys, and/or metabolism in liver, or through other routes such as saliva, milk, sweat, etc. The clearance associated with the kidney is called the renal clearance (C1r), and the clearance associated with other routes including metabolism is known as non-renal... 

Pithavala YK, Soria I and Zimmerman CL (1997) Use of the Deconvolution Principle in the Estimation of Absorption and Pre-Systemic Intestinal Elimination of Drugs. Drug Metab Dispos 25 pp 1260-1265. 

The hydrophobic interior of the phospholipid membrane constitutes a diffusion barrier virtually impermeable for charged particles. Apolar particles, however, penetrate the membrane easily. This is of major importance with respect to the absorption, distribution, and elimination of drugs. 

K4. Keen, P., Effect of binding to plasma proteins on the distribution, activity and elimination of drugs. In Concepts in Biochemical Pharmacology (B. B. Brodie and J. R. Gillette, eds.). Handbook of Experimental Pharmacology, Vol. 28, Part 1, pp. 213-233. Springer-Verlag, Berlin and New York, 1971. 

MlO. Martin, B. K., Kinetics of elimination of drugs possessing high affinity for the plasma proteins. Nature (London) 207, 959-960 (1965). 

Flumazenil is a highly extracted drug. Clearance of flumazenil occurs primarily by hepatic metabolism and is dependent on hepatic blood flow. In healthy volunteers, total clearance ranges from 0.7 to 1.3 L/h/kg, with less than 1% of the administered dose eliminated unchanged in urine. Elimination of drug is essentially complete within 72 hours, with 90% to 95% appearing in urine and 5% to 10% in feces. 

As an employer who has to manage safety critical applications, do not use drug tests to test for impairment. It does not work. This strategy leads to the elimination of drug-free workers (in cases of false positives), and it also fails to catch workers who are impaired (false negatives). False negatives can lead to disasters. Use impairment tests such as that developed by Performance Factors Impairment tests are not intrusive, they are more cost effective and take less time to administer, and they test impairment rather than lifestyle. 

Decreased renal elimination of drugs and metabolites marked interindividual variation... 

Urine alkalinization is a treatment modality that increases elimination of poisons by the intravenous administration of sodium bicarbonate to produce urine with a pH of more than or equal to 7.5 and must be supported by high urine flow. This technique might be useful for the elimination of drugs with an acid pKa such as salicylates (but not recommended for phenobarbital intoxication for which multiple-dose activated charcoal is better), chlorpropamide, 2,4-dichlorophenoyacetic acid, diflunisal, fluoride, mecoprop, methotrexate. Complications include severe alkalemia, hypokalemia, hypocalcemia and coronary vasoconstriction. 

Both metabolism and excretion can be viewed as processes responsible for elimination of drug (parent and metabolite) from the body. Drug metabolism changes the chemical structure of a drug to produce a drug metabolite, which is frequently but not universally less pharmacologically active. Metabolism also renders the drug compound more water soluble and therefore more easily excreted. 

Elimination Reduced renal plasma flow Reduced glomerular filtration rate Decreased tubular secretion function Decreased renal elimination of drugs and metabolites marked interindividual variation... 

Phase II hepatic metabolism involves the conjugation of drugs ortheir metabolites to organic substrates. The elimination of drugs that undergo phase II metabo-... 

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