Clearance defined

SavTl, J., and Fadok, V., 2000, Corpse clearance defines the meaning of cell death. Nature 407 784-788. 

One widely used performance index of hemodialyzers is that of clearance, defined similarly to that of the human kidney. The clearance of a hemodialyzer is the conceptual volume of blood (cm inin ) from which a uremic substance is completely removed by hemodialysis. Let Qg (cm min ) be the blood flow rate through the dialyzer, Qjj fern min ) the dialysate flow rate, and Cg and Cj3 (mgem ) the concentrations of a uremic substance in the blood and the dialysate, respectively, with the subscripts i and o indicating values at the inlet and outlet, respectively. The rate of transfer of the substance in the dialyzer w (mgmin ) is then given as... 

Figure 6 Directional transport of pravastatin in Oatplb2/Mrp2 double transfectants in the apical direction (A), and comparison of in vivo biliary excretion clearance and in vitro transcellular transport clearance across the double transfectant (B). (A) Transcellular transport across the monolayers of MDCK II cells was determined in the basal-to-apical and the opposite direction. (B) The x axis represents CLint determined in vitro multiplied by /B and the scaling factor, and the y axis represents the in vivo biliary clearance defined for the blood ligand concentrations. The symbol ( ) represents data whose x axis values were corrected for the scaling factor (a = 17.9). The solid line represents the theoretical curve, and the symbol (o), the observed data. Source From Ref. 59.

Each molecule has its own hazard rate, and if we assume a constant volume of distribution V, each molecule will have its own clearance defined as CL = Vh. Then CL becomes a random variable, and there follows the distribution of h with expectation E[CL] = VE h = V/i/X. Regardless of the molecule s clearance, the systemic clearance may be obtained on the basis of the expected profile E [IV (f)] using either the plateau evaluation during a long-term infusion or the total area under the curve. Both evaluations give CL = V (ji 1)/A. Note that for p, = 1, the systemic clearance cannot be defined albeit individual molecular clearances exist. The discrepancy between E CL and CL is due to the randomness of the model parameter h. 

Clearance and volume of distribution are two separate and independent characteristics of a drug. They are closely correlated with physiologic mechanisms in the organism (thereby the term primary parameters). Clearance defines the body s ability to remove the drug, that is, by metabolism or by renal or biliary excretion. Volume of distribution is a measure of the physical interrelationship between the drug and body constituents, such as binding to plasma proteins or partition into muscle, tissue, or fat. 

A series of clinical outcome reports have demonstrated that measures of PD solute removal correlate with patient status and outcome. In particular, a multicenter prospective cohort study of 680 incident CAPD patients [Canada-United States (CANUSA) Study] showed that a decrease of 0.1 in weekly urea clearance (defined by Kt/V ,ea) was associated with a 5% increase in the relative risk of death. Similarly a decrease of 5L/wk/1.73m of total creatinine clearance (Cc,) was associated with a 7% increase in the risk for death. As a consequence of these studies, national guidefines from the United Kingdom, Australia, and the United States " have set standards of dialysis adequacy in terms of small solute removal. An estimate of adequacy is performed in all patients withm 6 to 8 weeks of commencement of dialysis. Further studies should be performed at least annually. ... 

In addition to the three parameters, clearance (CL), bioavailability (F), and volume of distribution (V) discussed previously, a fourth parameter, half-life ( 1/2), is also crucial in therapeutics. The decreasing order of importance of these four parameters is clearance, bioavailability, half-life, and volume. Clearance defines the dosing rate, bioavailability defines dose adjustment, and half-life defines the dosing interval. Volume of distribution defines the loading dose. 

There are no requirements saying that vias need to be filled with solder—sometimes they do, sometimes they do not. The size of the via and of the solder mask clearance defining the... 

Bearing radial clearance defines the relative translation or subluxation required for head/rim contact and the associated stripe wear patterns to occur. The results have implications towards the design of inq)lants that promote or discourage joint laxity through inq)lant subsidence. In addition, for ceramic bearings, microseparation testing provides a clinically relevant test that can differentiate between the wear of different ceramic materials which is not possible using conventional hip joint simulators. 

It is truly possible to imagine the characteristics of an ideal radiopharmaceutical only in the context of a specific disease and organ system to which it might be appHed. Apart from the physical factors related to the radioisotope used, the only general characteristic that is important in defining the efficacy of these materials is the macroscopic distribution in the body, or biodistribution. This time-dependent distribution at the organ level is a function of many parameters which may be divided into four categories factors related to deUvery of the radiopharmaceutical to a particular tissue factors related to the extraction of the compound from circulation factors related to retention of the compound by that tissue and factors deterrnined by clearance. The factors in the last set are rarely independent of the others. 

The clinical performance of a hemodialy2er is usually described in terms of clearance, a term having its roots in renal physiology, which is defined as the rate of solute removal divided by the inlet flow concentration as shown in equation 7, where Cl is clearance in ml,/min and all other terms are as defined previously except that, in deference to convention, flow rates are now expressed in minutes rather than seconds and feed side (/) is now synonymous with blood flow on the luminal side. 

Note that the numerator in each of the ratios in equation 7 represents the rate of solute removal from the patient. By mass balance, clearance is related to mass-transfer coefficient Kq as defined eadier in equations 3, 4, and 5, and where each of the three expressions equal rate of mass removal in g/s. 

Katz (R-16) also siwdied wave-plate impingement separators (Fig. 14-Il0b) made up of 90° formed arcs with an 11.1-mm (0.44-iu) radius auda 3.8-mm (0.15-iu) clearance between sheets. The pressure drop is a function of system geometiy. The pressure drop for Katz s system and collection efficiency for seven waves are shown in Fig. 14-111. Katz used the Souders-Brown expression to define a design velocity for the gas between the waves ... 

Locations falling within this category can employ motors that are more economical than the other types discussed above. lEC 60079-14 has defined the basic requirements for such enclosures which are obviously less stringent than the others. In addition to maintaining specified creepages and clearances between the rotating and the stationary parts, the following are the two main requirements specified for such enclosures ... 

Special provisions are laid down in lEC 60079-0 and lEC 60079-1 for motors required for such locations in view of fluctuating degrees of humidity and temperature. Such locations are defined with a surface temperature limit of 150°C where coal dust can form a layer, or 450°C where it is not expected to form a layer. Otherwise, other details are generally the same as for flameproof motors type Ex d , according to lEC 60079-1. For variations in length of paths, gaps, widths, creepage and clearance distances, the reader should consult these Standards. 

Clearance is defined as the fraction of the volume of distribution Vp that is cleared of the drug per unit of time. In the case of elimination from the kidneys, the clearance provides a measure for the effectiveness of renal elimination with respect to the dmg under study. 

The clearance of the drug from the plasma is then defined from the dose D and the AUC ... 

Two types of diuretics are used for volume management in HF thiazides and loop diuretics. Thiazide diuretics such as hydrochlorothiazide, chlorthalidone, and metolazone block sodium and chloride reabsorption in the distal convoluted tubule. Thiazides are weaker than loop diuretics in terms of effecting an increase in urine output and therefore are not utilized frequently as monotherapy in HF. They are optimally suited for patients with hypertension who have mild congestion. Additionally, the action of thiazides is limited in patients with renal insufficiency (creatinine clearance less than 30 mL/minute) due to reduced secretion into their site of action. An exception is metolazone, which retains its potent action in patients with renal dysfunction. Metolazone is often used in combination with loop diuretics when patients exhibit diuretic resistance, defined as edema unresponsive to loop diuretics alone. 

FIGURE 56-2. Treatment algorithm for gout and hyperuricemia. Renal insufficiency is defined as an estimated creatinine clearance (CrCI) of less than 30 mL/minute. IA, Intraarticular NSAID, nonsteroidal anti-inflammatory drug. 

Compartment numbers shown in lower right corners are used to define clearance pathways. The clearance pathways as well as the compartment abbreviations are presented in Table 3-5. 

GIT, is considered to be lost from the absorption site, as is metabolic clearance and sequestration in various cell types and membranes (72,14). It is clear from Scheme I that the relative rates of the various processes will define the bioavailable fraction of the dose and understanding those factors which control pulmonary absorption kinetics is obviously the key to enhancing bioavailability via the lung. In a recent book (75) the molecular dependence of lung binding and metabolism was considered alongside the parallel processes of absorption, clearance and dissolution in the lung (14). Some key features of this work will be repeated as it relates to the systemic delivery of polypeptides. 

A clearance rate is defined as the volume of blood or plasma completely cleared of drug per unit time. It is a useful way to describe drug elimination because it is related to blood or plasma perfusion of various organs... 

The intrinsic clearance of an organ is different from the value we normally think of as the clearance of the organ. The clearance of the organ is defined as the rate of loss in relation to the incoming concentration, whereas the intrinsic clearance is defined as the rate of loss in relation to the organ concentration (or exiting concentration). In addition, it is also clear that, of the... 

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