Clearance total body

Data from both in vivo and in vitro systems showed PbTx-3 to have an intermediate extraction ratio, indicating in vivo clearance of PbTx-3 was equally dependent upon liver blood flow and the activity of toxin-metabolizing enzymes. Studies on the effects of varying flow rates and metabolism on the total body clearance of PbTx-3 are planned. Finally, comparison of in vivo metabolism data to those derived from in vitro metabolism in isolated perfused livers and isolated hepatocytes suggested that in vitro systems accurately reflect in vivo metabolic processes and can be used to predict the toxicokinetic parameters of PbTx-3. 

CF patients have a larger volume of distribution and enhanced total body clearance of many antibiotics, which often results in the need for higher doses to attain target levels. 

CF patients have larger volumes of distribution of many antibiotics due to an increased ratio of lean body mass to total body mass and lower fat stores. CF patients also have an enhanced total body clearance, although the exact mechanism has not been determined. Increased renal clearance, increased glomerular filtration rate, decreased protein binding, increased tubular secretion, decreased tubular reabsorption, extrarenal elimination, and increased metabolism have all been proposed as possible reasons for the increased clearance. 

BA, bioavailability CL, total body clearance CrCI, creatinine clearance CYP450, cytochrome P-450 ER, extended-release IR, immediate-release LA, long-acting PPI, proton pump inhibitor Sign., significantly SR, sustained-release TD, transdermal. 

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 ... 

Studies interested in the determination of macro pharmacokinetic parameters, such as total body clearance or the apparent volume of distribution, can be readily calculated from polyexponential equations such as Eq. (9) without assignment of a specific model structure. Parameters (i.e., Ah Xt) associated with such an equation are initially estimated by the method of residuals followed by nonlinear least squares regression analyses [30],... 

The total body clearance (CLl[)U ) of the drug in this patient was approximately... 

The answer is e. (Hardman, p 21J The fraction of a drug dose absorbed after oral administration is affected by a wide variety of factors that can strongly influence the peak blood levels and the time to peak blood concentration. The Vd and the total body clearance (Vd x first-order fte) also are important in determining the amount of drug that reaches the target tissue. Only the area under the blood concentration-time curve, however, reflects absorption, distribution, metabolism, and excretion factors it is the most reliable and popular method of evaluating bioavailability... 

CLl(Jtai —total body clearance cm—centimeter Cn—cyanide... 

After single-dose i.v. administration, total body clearance appears two- to four-fold higher in cancer patients than in healthy subjects, although elimination half-life (3.3-5.7 h) was similar in both groups. 

If the relationship between CLcr and the kinetic parameters of a drug (i.e., total body clearance [CL] and elimination rate constant [k]) is known, these data should be used to individualize drug therapy (Table 77-3). 

TABLE 77-3 Relationship between Creatinine Clearance and Total-Body Clearance and Terminal Elimination Rate Constant of Selected Drugs ... 

Drag Elimination Rate Constant Total Body Clearance... 

CL, total-body clearance CLcr, creatinine clearance k, elimination rate constant. 

The ratio (Q) of the estimated elimination rate constant or total body clearance relative to normal renal function is used to determine the dose or dosing interval alterations needed (CLfaii is the clearance with impaired renal function). 

In general, peritoneal dialysis is less effective in removing drugs than hemodialysis and, in fact, does not contribute substantially to total body clearance. 

The rate of total body clearance accounted for by the liver. 

The rate of total body clearance accounted for by the kidney. Its magnitude is determined by the net effects of glomerular filtration, tubular secretion and reabsorption, renal blood flow, and protein binding. 

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. 

Because the time function of drug concentration is dependent on the rate at which the drug is cleared from the hypothetical "volume," the AUC function is dependent on total body clearance, CL ... 

Key AUC Area under the curve, Cmax maximal serum concentrations, Tmax time to reach peak concentrations, Vd volume distribution, K rate constant for elimination, T2 Elimination half-life, and CIT Total body clearance time. (Wojcicki et al. 1995)... 

Aspirin Aspirin is rapidly hydrolyzed in plasma to salicylic acid with a half-life of 20 minutes. Plasma levels of aspirin are essentially undetectable 2 to 2.5 hours after dosing, and peak salicylic acid concentration occurs 1 hour (range, 0.5 to 2 hours) after aspirin administration. Salicylic acid is primarily conjugated in the liver to form a number of minor metabolites. Salicylate metabolism is saturable and the total body clearance decreases at higher serum concentrations. 

Excretion - Total body clearance is about 5.1 mL/min/kg (0.31 L/h/kg) for infusion doses 40 mcg/kg/min or less. The terminal elimination half-life of argatroban ranges between 39 and 51 minutes. Argatroban is excreted... 

Half-life and total body clearance depend on renal function ... 

Acyclovir Half-Life and Total Body Clearance Based on Renal... 

Metabolism/Excretion Zalcitabine is phosphorylated intracellularly to zalcitabine triphosphate, the active substrate for HIV-reverse transcriptase. Concentrations of zalcitabine triphosphate are too low for quantitation. Metabolism has not been fully evaluated. Zalcitabine does not appear to undergo a significant degree of metabolism by the liver. Renal excretion appears to be the primary route of elimination, and accounted for approximately 70% of an orally administered dose within 24 hours after dosing. The mean elimination half-life is 2 hours. Total body clearance following an IV dose averages 285 mL/min. Less than 10% of a dose... 

Patients younger than 3 months of age - The half-life was about 13 hours. In neonates 14 days of age or less, bioavailability was greater, total body clearance was slower, and half-life was longer than in pediatric patients more than 14 days old. 

The most significant metabolite of letrozole (3) is its secondary alcohol metabolite (SAM) 23 (Scheme 3.4). Biotransformation of letrozole is the main elimination mechanism, with the glucuronide conjugate of the secondary alcohol metabolite (24) being the prominent species found in urine. However, the total body clearance of letrozole is slow (2.21 L/h). Its elimination half-life is long, at 42 h. Letrozole and its metabolites are excreted mainly via the kidneys. 

Total body clearance ( what goes out ) is given by the apparent volume of distribution (1) x elimination rate constant (A ei) (as we have seen above, is measured in litres, and A ei as a fraction of 1, per unit time. A A ei of 0.1 implies that 1/lOth of a body s load of drug is cleared each hour). Clearance therefore has units of volume per unit time - put in another way it means the fraction of the total Vd cleared of drug per unit time. 

Total body clearance Reduced Increased Near adult pattern ... 

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