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Chapter: Medicine Study Notes : Pharmacology

Clearance (Cl) - Pharmacokinetics

Clearance of drug corresponds to the volume of plasma that appears to be cleared of its drug in unit time e.g. mls/min, l/hr.

Clearance (Cl)


·        = Elimination


·        Clearance of drug corresponds to the volume of plasma that appears to be cleared of its drug in unit time e.g. mls/min, l/hr.


·        Represents the size of the plug hole, rate of elimination (= rate of clearance) is the flow through the plug hole


·        Depends on rate at which drug is transported to the organ of elimination and the efficiency of the eliminating organ in removing the drug


·        Clearance = rate of elimination/drug concentration (as long as not saturable elimination, eg phyentoin, alcohol)

·        Clearance can be:

o   Concentration dependent/ Capacity limited: saturable metabolic pathway (eg phenytoin)


o   Flow-dependent: organ elimination rate = concentration * flow * extraction ratio (fraction cleared on each pass through the organ). Eg will be eliminated on 1st pass Þ elimination dependent on blood flow. If Heart failure ® ­vasoconstriction to maintain blood flow ® ¯liver flow


o   ®¯elimination (eg lignocaine, propranolol). Total body clearance can‟t exceed cardiac output (5 l/min)


·        Clearance and Volume of Distribution are independent of each other, but T½ is dependent on both


·        Maintenance Dose = clearance * desired concentration

·        Compartments:

o   One or multi compartment models

o   Ka = absorption into compartment

o   Ke = elimination from compartment

Linear kinetics


·        First order kinetics: rate of transport or elimination proportional to drug concentration in the compartment


·        Zero order kinetics: elimination has maximum value ® rate is non-linear and it‟s a capacity limited process. Eg alcohol is metabolised at 10 ml/hr. Beyond this the enzyme metabolism is swamped. So if dose rate is greater than clearance rate, then a small increase in dose rate leads to a dramatic increase in plasma concentration (ie accumulation)


Michaelis-Menten kinetics


·        For a drug that undergoes zero-order elimination, when the concentration is low enough, elimination no longer occurs at its maximum rate (V max) but at a rate dependent on but not proportional to the plasma concentration. As the concentration reaches ½ the maximum rate (km), first order elimination occurs


·        So, elimination will increase with increasing dose, but not proportional to the dose

·        Zero-order kinetics will be approached ® risk of accumulation

·        Issue for any drug having zero-order kinetics within its therapeutic range

·        E.g. salicylic acid (especially in overdose), phenytoin, alcohol


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