Clearance of drug

Factors known to influence the clearance of drugs from interstitial sites, following extravasation or parenteral interstitial or transepithelial administration, include size and surface characteristics of particles, formulation medium, the composition and pH of the interstitial fluid, and disease within the interstitium. Studies indicate that soluble macromolecules smaller than 30 nm can enter the lymphatic system, whereas particulate materials larger than 50 nm are retained in the interstitial sites and serve as a sustained-release depot. The use of lipids or an oil in a formulation and the presence of a negative surface charge all appear to... 

KS Pang, M Rowland. Hepatic clearance of drugs. I. Theoretical considerations of a well-stirred model and a parallel tube model. Influence of hepatic blood flow, plasma and blood cell binding, and the hepatocellular enzymatic activity on hepatic drug clearance. J Pharmacokin Biopharm 5/6 625-653, 1977. 

CKD may alter nonrenal clearance of drugs as the result of changes in cytochrome P450-mediated metabolism in the hver and other organs. The clinical reductions in nonrenal clearance in CKD are generally proportional to the reductions in glomerular filtration rate (Table 77-1). 

Clearance of drug occurs by the perfusion of blood to the organs of extraction. Extraction (E) refers to the proportion of drug presented to the organ which is removed irreversibly (excreted) or altered to a different chemical form (metabolism). Clearance (Cl) is therefore related to the flow of blood through the organ (Q) and is expressed by the formula ... 

Clearance of drug normally occurs from the liver and kidneys and it is an important assumption that only free (i. e. not protein bound) dmg is available for clearance. A diagram of the interaction of the major clearance processes is shown in Figure 5.1. 

In the broadest sense, total (systemic) clearance is the clearance of drug by all routes. Total (systemic) clearance (Cl) can be calculated by either of the equations given below ... 

Interferons reduce the activity of hepatic cytochrome P450 enzymes and decrease the clearance of drugs such as theophylline. Their effects may be additive with other drugs that have neurotoxic, hematotoxic or cardiotoxic activity. 

Because the kidney is the major organ for clearance of drugs from the body, the age-related decline of renal functional capacity is very important. The decline in creatinine clearance occurs in about two thirds of the population. It is important to note that this decline is not reflected in an equivalent rise in serum creatinine because the production of creatinine is... 

The finding that race and diet may affect the clearance of drugs such as antipyrine is such an example. Thus, meat-eating Caucasians have a significantly greater clearance and a shorter plasma half-life for antipyrine than Asian vegetarians. However, the relative importance of race versus diet as contributions to those differences is not clear. 

Unlike most plasma proteins and red blood cells, the metabolism and disposition of plasma lipoproteins is highly regulated and mediated in part by specific receptors located at discreet sites around the body. The concentrations of plasma lipoproteins in the blood can also vary significantly (up to tenfold) as a function of diet, disease, and both within and between healthy individuals. The implications, therefore, for the clearance of drug molecules associated with these plasma lipoproteins are considerable but have not been clearly defined. 

Levy G. 1982. Gastrointestinal clearance of drugs with activated charcoal. N E Journal Med 307 676-677. 

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