Distribution clearance

The rate of transport from a certain compartment is governed by the concentration in that compartment and a proportionality constant, denoted (elimination or distribution) clearance (dimension volmne time" ) as formulated below. 

When a drug is administered intravenously into the circulation the compound undergoes distribution into tissues etc. and clearance. For a drug that undergoes rapid distribution a simple model can explain the three important pharmacokinetic terms volume of distribution, clearance and half-life. 

Revising Individual Estimates of Volume of Distribution Clearance... 

The clinical development stage comprises three distinct components or phases (I, II, and III), and culminates in the filing of the NDA/MAA. Each phase involves process scale-up, pharmacokinetics, drug delivery, and drug safety activities. During phase I clinical development, the compound s safety and pharmacokinetic profile is defined. The determination of maximum concentration at steady state (Cmax), area under the plasma concentration time curve (AUC), elimination half-life, volume of distribution, clearance and excretion, and potential for drug accumulation is made in addition to studies that provide estimates of efficacious doses. Dose levels typically... 

Pharmacological properties (serum binding, distribution, clearance, half-life, etc.) Synthetic accessibility, simplicity, patentability Many of these properties may be influenced by the nonspecific affinity of the compound for host proteins however, these properties are not generally predictable from target choice at this time. Size, shape, and amino acid composition of the inhibitorbinding site may influence the chemical classes of inhibitors, as well as the achievable selectivity. 

Many of the drug monographs contain a new section entitled Disposition in the Body. This section details die absorption, distribution, and excretion of the drug, notes the major metabolites and therapeutic and toxic plasma concentrations, and gives values for pharmacokinetic parameters such as half-life, volume of distribution, clearance, and protein binding. In addition, abstracts from published clinical studies and case histories are included. 

Clearance is the parameter that relates the drug concentration in a cavity to the rate of its elimination. Clearance multiplied by concentration equals the rate of elimination. Units of clearance are expressed in volume per unit of time. The half-life is then expressed as T /2 (0.693 x volume of distribution)/clearance. The half-life... 

In vitro antifungal activities evaluation for sampangine metabolites demonstrated comparable activities to sampangine. However, an in vivo efficacy study revealed that SAh 2 is inactive. The antifungal activity profile of sampangine metabolites led us to conclude that metabolism per se is not the cause for the in vivo inactivity of sampangine, hence, further studies on the other pharmacokinetic parameters (bioavailability, distribution, clearance, etc.) will be necessary. 

The distribution clearance is a distribution parameter that, when multiplied by the AUC of the drug concentration response, gives the total amount of drug returned from the peripheral distribution space. The distribution clearance is directly related to the distribution function, h(t), by... 

For drugs with a linear disposition, the clearance, the generalized elimination clearance, and the distribution clearance are simply related by... 

Papich and Riviere report marked variability in aminoglycoside pharmacokinetics (distribution, clearance, and half-life) with altered physiologic or pathologic states, including pregnancy, obesity, dehydration, immaturity, sepsis, endotoxemia, and renal disease. The latter influence is predictable from the fact that body clearance is dependent almost entirely on renal excretion. Martin-Jimenez and Riviere concluded that aminoglycoside pharmacokinetics can be predicted across species by population pharmacokinetic modeling. ... 

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