Dose clearance

Rate of dosing/Clearance Steady-state concentration Therapeutic response... 

Thus, if the dose, clearance, and AUC are known, bioavailability can be determined from the relationship shown in Eq. (3.16) ... 

This is usually referred to as first-order elimination. When clearance is first-order, it can be estimated by calculating the area under the curve (AUC) of the time-concentration profile after a dose. Clearance is calculated from the dose divided by the AUC. 

The most widely used approach to evaluate plasma (total) CL involves IV administration of a single dose of a chug and measuring its plasma concentration at different time points, as shown in Fig. 2.2. In this manner, the calculated clearance will not be confounded by complex absorption and distribution phenomena which commonly occur during oral dosing. Clearance is derived from the equation (Rowland and Tozer, 1995)... 

Maintenance dose = (clearance) X (steady- ate plasma concentration)... 

AUC is a frequency distribution of the number of molecules within the body versus time. When measured out to infinity (< ), the AUC value (AUCo a) represents the total drug exposure. Its value is unaffected by the rate of absorption (assuming linear kinetics) but is affected by dose, clearance and bioavailability. Bioavailability is calculated by comparing the total amount of drug in the body (AUC) following administration by a non-i.v. route with that obtained following i.v. administration (100%), corrected for dose. 

Quetiapine exhibits dose proportional linear pharmacokinetics within the clinical dose range with accumulation that is predictable on multiple dosing. Clearance of quetiapine is largely through hepatic metabolism with a... 

Because IFNs induce long-lasting cellular effects, their activities are poorly predicted from usual pharmacokinetic measures. After intravenous dosing, clearance of IFN from plasma occurs in a complex manner. With subcutaneous or intramuscular dosing, the plasma elimination t of IFN-a ranges from 3 to 8 hours, largely due to distribution to the tissues, cellular uptake, and catabolism in the kidney and liver. Negligible amounts are excreted in the urine. Clearance of IFN-a is reduced by 7Wc in dialysis patients. 

Few drugs are given Intravenously. This means that for most drugs the fraction which is absorbed intact into the circulation is often very much less than unity. This fraction, F, is referred to as the bioavailability. The bioavailability of oral formulations is often established in special studies (usually cross-over studies in healthy volunteers) in which the area under the plasma - concentration time curve (AUC) of the oral formulation is compared with that of an intravenous formulation. The bioavailability can then be calculated as the ratio of AUC to dose delivered for the oral formulation to the corresponding ratio for the intravenous formulation. Since the total amount eliminated from the body is equal to the clearance times the AUC, and since the total amount eliminated equals the amount absorbed, which is simply the dose times the bioavailability, so dose, AUC, bioavailability and clearance are linked by the formula, F x Dose = Clearance x AUC. For many drugs the bioavailability and clearance are independent of the dose administered. This property is referred to as dose-proportionality and is... 

With a diameter ratio of 0.9-0.98, the helical ribbon belongs to the dose-clearance category of impellers. 

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