Clearance total

Clearance is the volume remaining in a cylinder end when the piston is at the end of its stroke. This is die sum of the volume between the head of the cylinder and the piston, and the volume under tlie valve seats. The total clearance is expressed in percent of the total piston displacement, normally between 4 and 30%. 

For double-acting cylinders, % clearance is based on total clearance volume for both the head end and crank end of the cylinder X 100 divided by the total nel piston displacement. The head and crank end % clearance values will be different due to the presence of the piston rod in the crank end of the cylinder. The % clearance values are available from manufacturers for their cylinders. The values range from about 8% for large 36-in. cylinders to 40% for small 3-and 4-in. cylinders. Each cylinder style is different. 

The total clearance increases in proportion to the free plasma fraction while free plasma clearance remains constant. 

Dost FH (1954) [Half value time and total clearance.] Halbwertszeit und totale Clearance. Z Gesamte Inn Med 9 Jun 1 (11 ) 546—51... 

Drugs can be cleared from the body by metabolism as well as renal excretion, and when this occurs it is not possible to measure directly the amount cleared by metabolism. However, the total clearance rate (TCR), or total body clearance, of the drug can be calculated from its pharmacokinetic parameters using the following equation ... 

Organ clearances are usually based on in vivo rather than in vitro studies. Drug metabolic parameters, Vm and Km, can be estimated from in vitro hepatic enzyme and hepatocyte preparations [53], Knowledge of total clearance and fractional... 

Total clearance during dialysis can be calculated as the sum of the patient s residual clearance during the interdialytic period (CLRES) and dialyzer clearance (CLD) ... 

I] is inhibitor concentration at steady state, CL/(c) is the formation clearance (for each metabolite it is calculated according to CL/(c) = fm x CLt, where CLt is the total clearance of the substrate from the body and fm is the fraction of dose recovered in the urine as a specific metabolite) to the metabolite in the absence of the inhibitor, and CLj(i) is the formation clearance to the metabolite in the presence of inhibitor. 

When a preparation of phenytoin was administered to a patient, the volume of distribution was found to be 70 liters, and the half-life of elimination was 1.5 hours. What is the total clearance of phenytoin ... 

Gentamicin is shown to have a Vd of 0.25 L per kg of the body weight. If the weight of the patient is 132 lb, and the elimination rate constant is 0.33 hour 1, what is the total clearance of gentamicin ... 

The term clearance is used here in the sense of total body clearance and is analogous to the term renal clearance. The body as a whole is regarded as acting as a xenobiotic-eliminating system, where the rate of elimination divided by the average plasma concentration of the compound is the total body clearance. Here clearance is calculated (25) by dividing the administered dose of the substance by the area under the plasma concentrationtime curve produced by that dose. This pharmacokinetic parameter, as well as others presented in this publication, was calculated by the use of the MLAB on-line computer system established at the National Institutes of Health by Knott and Reece (26). Similar to t the total clearance is a composite of the individual clearances of the material by the various tissues of the body. 

Thus, for example, if a chemical is eliminated only by renal excretion and hepatic metabolism, total clearance is a composite... 

The rate of metabolism of nicotine can be determined by measnring blood levels after administration of a known dose of nicotine (Table 1) (Hukkanen et al. 2005c). Total clearance of nicotine averages about 1200 ml min . Nonrenal clearance represents about 70% of liver blood flow. Assuming most nicotine is metabolized by the hver, this means that about 70% of the drug is extracted from blood in each pass through the hver. 

Clearance of nicotine is decreased in the elderly (age >65) compared to adults (Molander et al. 2001). Total clearance was lower by 23%, and renal clearance lower by 49% in the elderly compared to yonng adults. Lower nicotine metabolism in the elderly may be contribnted to by rednced liver blood flow, since no decrease in CYP2A6 protein levels or nicotine metabolism in liver microsomes due to age has been detected (Messina et al. 1997). No differences in steady-state nicotine plasma levels or estimated plasma clearance valnes were detected in three age gronps (18-39, 40-59, and 60-69 years) nsing patches with the same nicotine content (Gonrlay and Benowitz 1996). The volnme of distribntion of nicotine is lower in older snbjects due to a decrease in lean body mass (Molander et al. 2001). 

Renal clearance of cotinine is much less than the glomerular filtration rate (Benowitz et al. 2008b). Since cotinine is not appreciably protein bound, this indicates extensive tnbnlar reabsorption. Renal clearance of cotinine can be enhanced by np to 50% with extreme urinary acidification. Cotinine excretion is less influenced by urinary pH than nicotine becanse it is less basic and, therefore, is primarily in the unionized form within the physiological pH range. As is the case for nicotine, the rate of excretion of cotinine is influenced by urinary flow rate. Renal excretion of cotinine is a minor route of elimination, averaging about 12% of total clearance. In contrast, 100% of nicotine Ai -oxide and 63% of 3 -hydroxycotinine are excreted unchanged in the urine (Benowitz and Jacob 2001 Park et al. 1993). 

Another term which is important in pharmacokinetics is the half-life (fi/2) of a drug. This value is related to the Vd and the total clearance. If it is assumed that the body is a single compartment in which the size of the compartment equals the Vd, the fi/2 may be calculated from the equation ... 

Pharmacokinetics When administered intravenously, ICG rapidly binds to plasma proteins and is exclusively cleared by the liver, and subsequently secreted into the bile [8]. This forms the basis of the use of ICG for monitoring hepatic blood flow and function. Two pharmacokinetics models, a monoexponential decay, which describes the initial rapid clearance of ICG with a half-life of about 3 minutes (Eq. (1)) and a bi-exponential model, which incorporates the secondary phase clearance with a longer half-life (Eq. (2)), describe total clearance of ICG from plasma [ 132]. For real-time measurements by continuous organ function monitoring, the mono-exponential decay is preferred. 

In humans, for all these compounds, Vp is about 0.15-0.27 L kg (consistent with the extracellular volume which, in humans, is about 0.25 L kg ), Tj/ja is 4- 10min,Ti/2 is between 100 and 130 min and total clearance is 1-2 mLmin kg [5]. These compounds are characterized by a rapid distribution about 70% of the injected dose is cleared from plasma (diffusion and excretion) within 2-5 minutes after injection [5]. Because of their high hydrophilicity, they do not enter the intracellular space to a significant extent. 

The smaller the volume of distribution or the larger the total clearance, the shorter is the half-life. 

Pharmacokinetics In healthy adults treated with IV doses of iron sucrose, its iron component exhibits first order kinetics with an elimination half-life of 6 hours, total clearance of 1.2 L/h, non-steady-state apparent volume of distribution of 10 L, and steady-state apparent volume of distribution of 7.9 L. 

Metaboiism/Excretion-The terminal elimination half-life for drug bound iron was approximately 1 hour, varying by dose but not by rate of administration. Total clearance was 3.02 to 5.35 L/h. In vitro, less than 1 % of the iron species within sodium ferric gluconate complex can be dialyzed through membranes with pore sizes corresponding to 12,000 to 14,000 daltons over a period of up to 270 minutes. 

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. 

Hepatic function impairment Mean total clearance is decreased to 40% to 60% of normal in patients with moderate liver dysfunction and to 25% of normal in patients with severe liver dysfunction compared with age-matched healthy subjects. This results in a prolongation of the half-life from 0.8 hours in healthy subjects to 1.3 hours in patients with moderate hepatic impairment and 2.4 hours in severely impaired patients. 

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