Clearance concepts

By applying an extension of the clearance concept 30, 31), in vitro metabolism was used to predict in vivo toxin elimination. Hepatocytes were incubated with 0.5 to 10 pg unlabeled PbTx-3 containing 0.1 pg radiolabeled toxin as tracer. Disappearance of parent compound and the appearance of metabolites were measured by HPLC equipped with a Radiomatic isotope detector. (1.6 nmol/min/g liver)... 

Reigner, B.G., F.Y. Bois, and T.N. Nozer. 1992a. Assessment of pentachlorophenol exposure in humans using the clearance concept. Human Exper. Toxicol. 11 17-26. 

Rowland, M., Benet, L.Z. and Graham, G.G. (1973) Clearance concepts in pharmacokinetics. Journal of Pharmacokinetics and Biopharmaceutics,... 

Drug clearance principles are similar to the clearance concepts of renal physiology. Clearance of a drug is the factor that predicts the rate of elimination in relation to the drug concentration ... 

We examined the biodistribution of cationic liposomes/pDNA complex following intravenous injection in mice and pharmacokinetically analyzed the data based on the clearance concept (Mahato etal., 1995a, 1997). These analyses showed that the pharmacokinetics of 32P-pDNA complexes depend on their mixing (charge) ratio, the type of cationic and helper lipids (Mahato et al., 1998). When analyzed using radioactivity counting following the injection of the complex prepared with 32P-pDNA, the tissue uptake clearance per g... 

Zuidema J, van Ginneken CA (1983) Clearance concept in salivary drug excretion. Part I theory. Pharm Acta Helv 58(3) 88—93... 

Rowland M, Benet LZ, Graham GG. Clearance concepts in pharmacokinetics. J Pharmacokinet Biopharm 1973 1 123-136. 

Therefore, the power-law behavior itself is a self-similar phenomenon, i.e., doubling of the time is matched by a specific fractional reduction of the function, which is independent of the chosen starting time self-similarity, independent of scale is equivalent to a statement that the process is fractal. Although not all power-law relationships are due to fractals, the existence of such a relationship should alert the observer to seriously consider whether the system is self-similar. The dimensionless character of a is unique. It might be a reflection of the fractal nature of the body (both in terms of structure and function) and it can also be linked with species invariance. This means that a can be found to be similar in various species. Moreover, a could also be thought of as the reflection of a combination of structure of the body (capillaries plus eliminating organs) and function (diffusion characteristics plus clearance concepts). 

Shoker AS (1994) Application of the clearance concept to hy-ponatremic and hypematremic disorders a phenomenological analysis. Clin Chem 40 1220-1227 Suki W, Rector FC, Seldin DW (1965) The site of action of furosemide and other sulfonamide diuretics in the dog. J Clin Invest 44 1458-1469... 

The clearance concept has been used in defining the pharmacokinetics of drugs since the mid-1970s. " The elearanee eoneept is based in physiology, where it is used as a measure of renal funetion (ereatinine elear-ance). Creatinine is formed from muscle breakdown at a constant rate, and thus a constant creatinine concentration in plasma results. The magnitude of this concentration is dependent on the elimination rate of ereatinine and the size of the muscle pool (formation rate). By measuring the plasma concentration and the renal excretion of ereatinine, renal clearance can be estimated and thereby kidney function indicated, as ereatinine is mainly filtered into the urine... 

The general principle that is used to select the appropriate maintenance dose and dosing interval for the average patient is as follows to maintain a target concentration at the steady state, the rate of drug administration should be equal to the rate of elimination. This can be expressed by the following equation [Eq. (1)] using the clearance concept ... 

The clearance concept can successfully be applied to analyze metabolite kinetics in blood (13). It can, by analogy, be used for the kinetics of the active moiety after prodrug administration. As with the compartmental approach, care must be taken when prodrug transformation occurs during first pass and/or prodrug excretion is important after it reaches the systemic circulation. Here again, some differences with metabolite kinetics occur in the function of two different aspects ... 

The Scottish findings arguably represent a worst-case scenario, and areas with lower tap water Pb levels would presumably show a lower fractional contribution to body lead, but Bois et al. (1989) reported that the use of clearance concepts for tap water Pb consumption in children supported a U.S. MCL of 10 pg/1 since the then-current value of 50 pg/1 made water Pb a major Pb intake source. Elwood et al. (1984) found that Welsh women randomly sampled with respect to PbB and various sources of environmental Pb could sometimes have a higher exposure to water Pb than to the element in ambient air. 

Bois, Frederick Y., Thomas N. Tozer, Lauren Zeise, et al. 1989. Application of Clearance Concepts to the Assessment of Exposure to Lead in Drinking Water. American Journal of Public Elealth 79 827-831. 

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