Drug Clearance

Defination
• Drug clearance is defined as the volume of
plasma cleared of a drug over a specified time
period. Thus, the units of measurement
for drug clearance is in volume/time
• CL = Rate of elimination / Concentration of
drug in fluid
 Type of Clearance
• Renal clearance ( removal of drug by kidney)
• Hepatic clearance ( removal of drug by liver)
• Extra renal clearance ( removal of drug by
other organs e.g slivary, pulmonary,
mammary, skin / dermal)
• Systemic clearance ( summation of all
individual organ clearance)
 Total Body Clearance
• Total body clearance is equal to the
sum clearance of the substance by each organ
(e.g., renal clearance + hepatic clearance +
lung clearance = total body clearance)
• Renal clearance = Ke VD
• Lungs Clearance = Kl VD
• Hepatic clearance = Km VD
• Body Clearance = Ke VD+ Kl VD + Km VD
• = ( Ke + Kl + Km)VD = KVD
 Elimination
• Irreversible removal of drug from the body by
all routes of elimination
• drug elimination is divided into
– excretion (removal of intact drug)
– biotransformation
• First order elimination constant proportion of
drug is eliminated per unit time ( directly
proportional to concentration of drug)
• Zero order constant amount of drug is
eliminated per unit time ( independent of
concentration)
 Half Life
• time taken by the concentration of drug in the
plasma or the total amount in the body to be
reduced by 50 %
• phases of half life
– Alpha Phase ( plasma / distribution half life)
– Beta Phase ( tissue / elimination half life)
• Half life of the drug directly proportion to the
volume of distribution and inversely
proportion to the clearance
T ½ = 0.693 / K
• factors increasing half life
– decrease renal plasma flow
– addition of second drug
– decrease excretion ratio
– decrease metabolism
• Idiosyncracy
• drug tolerance
• tachyphylaxis
• drug dependence
( Book)