Half Life (T½)

Half Life (T½)

·        Time for drug concentration to decline by half Þ influences dosing interval

·        Is dependent on clearance and volume of distribution:

§  Vd = T½ * clearance / 0.693

·        Rate at which drug leaves the body is dependent on Cl & Vd. In one compartment model: Ke = Cl/Vd

·        = Measure of how the whole body handles the drug – how quickly it gets out

·        But it doesn‟t work in practice…

o  For slowly excreted drugs, 5 * T½ and it will be eliminated for practical purposes 

o  But for anaesthetic drugs that you want to switch on and off quickly the therapeutic window is often in the redistribution phase – not the elimination phase. Need a more complex model where the drug redistributes to (then from) slow and fast compartments, as well as being excreted from blood ® context sensitive half-life. If drug is over infused, it builds up in other compartments and then takes a long time to wash out. So give a reducing amount over the duration of infusion as other compartments get saturated and stop „sucking it out‟ of blood