Drug elimination clearance

Drug Elimination Clearance (mL/kg/min) Approximate Duration of Action (minutes) Approximate Potency Relative to Tubocurarine... 

The effect of hemofiltration on drug elimination can be estimated from serum creatinine (SCr), age, and the MDRD-2 formula to predict the combined effect of filtration rate (eGFR = GFRresidual + HFR) on drug clearance and drug half-life during hemofiltration. 

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... 

Accelerated drug elimination is also a possible reason for failure and may occur in patients with cystic fibrosis or during pregnancy, when more rapid clearance or larger volumes of distribution may result in low serum concentrations, particularly for aminoglycosides. 

T or si Free fraction of highly plasma protein-bound drugs si Clearance and T t1/2 for some oxidatively metabolized drugs si Clearance and T t1/2 for drugs with high hepatic extraction ratios si Clearance and T t 2 for renally eliminated drugs and active metabolites... 

The terminator of drug action is, of course, elimination. Elimination is a composite of excretion (kidney, etc.) and biotransformation (metabolism). The primary measure of drug elimination from the whole body is clearance, CLt, defined as the volume of plasma fluid removed of drug per unit time. It is a direct measure of the loss of the drug from the system and can be calculated from Eq. (3.5) after IV administration of a dose of the drug. 

The clearance of a drug is usually defined as the rate of elimination of a compound in the urine relative to its concentration in the blood. In practice, the clearance value of a drug is usually determined for the kidney, liver, blood or any other tissue, and the total systemic clearance calculated from the sum of the clearance values for the individual tissues. For most drugs clearance is constant over the therapeutic range, so that the rate of drug elimination is directly proportional to the blood concentration. Some drugs, for example phenytoin, exhibit saturable or dose-dependent elimination so that the clearance will not be directly related to the plasma concentration in all cases. 

Renal function Impairment Drug elimination was related to GFR. Clearance was reduced approximately 20% in patients with moderate and severe renal impairment and was reduced approximately 80% in dialysis-dependent patients. 

What makes prediction of drug elimination complex are the multiple possible pathways involved which explain why there is no simple in vitro clearance assay which predicts in vivo clearance. Because oxidative metabolism plays a major role in drug elimination, microsomal clearance assays are often used as a first line screen with the assumption that if clearance is high in this in vitro assay it is likely to be high in vivo. This assumption is often, but not always true because, for example, plasma protein binding can limit the rate of in vivo metabolism. However, compounds which have a low clearance in hepatic microsomes can be cleared in vivo via other mechanisms (phase II metabolism, plasmatic errzymes). Occasionally, elimination is limited by hepatic blood flow, and other processes like biliary excretion are then involved. The conclusion is that the value of in vitro assays needs to be established for each chemical series before it can be used for compound optimization. 

L D. Excretion (A) and drug clearance (E) are factors involved in drug elimination, while absorption (B) describes the ability of a drug to cross membranes and enter the blood stream. Distribution (C) describes the ability of a drug to enter a variety of body compartments during its circulation in the blood. 

The total amount of drug eliminated is equal to the clearance time as a product of the AUC (i.e., clearance x AUC). This product is also co-equal to the amount that is absorbed (i.e., F x Dose) as is presented in Eq. (3.15) ... 

The pharmacokinetic term clearance (CT) best describes the efficiency of the elimination process. Clearance by an elimination organ (e.g., liver, kidney) is defined as the volume of blood, serum, or plasma that is totally cleared of drug per unit time. This term is additive the total body or systemic clearance of a drug is equal to the sum of the clearances by individual eliminating organs. Usually this is represented as the sum of renal and hepatic clearances CT = CT renal -I- CL hepatic. Clearance is constant and independent of serum concentration for drugs that are eliminated by first-order processes, and therefore may be considered proportionally constant between the rate of drug elimination and serum concentration. 

Clearance (Cl) and volumes of distribution (VD) are fundamental concepts in pharmacokinetics. Clearance is defined as the volume of plasma or blood cleared of the drug per unit time, and has the dimensions of volume per unit time (e.g. mL-min-1 or L-h-1). An alternative, and theoretically more useful, definition is the rate of drug elimination per unit drug concentration, and equals the product of the elimination constant and the volume of the compartment. The clearance from the central compartment is thus VVklO. Since e0=l, at t=0 equation 1 reduces to C(0)=A+B+C, which is the initial concentration in VI. Hence, Vl=Dose/(A+B-i-C). The clearance between compartments in one direction must equal the clearance in the reverse direction, i.e. Vl.K12=V2-k21 and VVkl3=V3-k31. This enables us to calculate V2 and V3. 

During chronic alcohol consumption, MEOS activity is induced. As a result, chronic alcohol consumption results in significant increases not only in ethanol metabolism but also in the clearance of other drugs eliminated by the cytochrome P450s that constitute the MEOS system, and in the generation of the toxic byproducts of cytochrome P450 reactions (toxins, free radicals, H202). 

Once die steady-state concentration is known, the rate of drug clearance determines how frequently the drug must be administered. Because most drug elimination systems do not achieve saturation under therapeutic dosing regimens, clearance is independent of plasma concentration of the drug. 

Clearance is defined as the proportionality factor that relates the rate of drug elimination to the blood or plasma drug concentration 16... 

In the above equation, the concentration term refers to drug concentration at steady state. The units of clearance are volume per unit time and, therefore, this parameter measures the volume of biological fluid, such as blood, that would have to have drug removed to account for drug elimination. Therefore, clearance is not a measure of the amount of drug removed. 

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