Clearance of drug is the rate of elimination by all routes of the concentration of drug in a biological fluid. Clearance is of great concern when considering the administration of a drug over time. Clearance does not refer to how much drug is being removed from the body but means the volume of fluid for example blood that would have to be completely free of drug to account for elimination. It is imperative to maintain steady state concentrations of drugs within a given range. Clearance is expressed as a volume per unit of time and is given by the equation CL = Rate of elimination / C( the concentration). It is assumed that for complete bioavailability the rate of drug elimination must equal the rate of drug administration, this can be represented by: Dosing = CL ( Css ) where CL is clearance and Css is steady state.
Clearance of drugs by different organs is summative and is given by the equation
CL(renal) + CL( Liver) + CL(other organs) = CL( systemic). The absolute clearance of drug is considered as a linear function of its concentration in plasma. In respect the elimination of drugs follows a first order kinetics that is a constant fraction of drug is eliminated per unit of time. For a single dose of with complete bioavailability and first order kinetics of elimination, the total systemic clearance is determined by CL = Dose / total concentration of drug in circulation.
Total clearance of drugs can be determined using the equation CL = Dose / AUC where AUC is the total area under the curve that describes the concentration of drug in the systemic circulation as a function of time.
Bioavailability
Bioavailability means the amount of drug that reaches the systemic circulation. This amount can be a fraction of the drug that entered the body initially. There many reasons for the reduction in the bioavailability of the drug. For example the drug may be metabolized by the liver or excreted by the bile; some drugs are absorbed from the gastrointestinal tract and will be inactivated by the liver before it reaches the general circulation for distribution to the needed site.