Clearance Flashcards
What is clearance and what are the units?
Clearance is the relationship between concentration and the rate of elimination of a drug from the body.
Units = L/h
What is the key factor determining size of clearance of a drug and what are the two main organs considered in clearance calculations?
Blood flow! The clearance cannot be more than the rate of blood flow to an organ.
Two main organs are Liver and Kidney.
The liver is the largest organ responsible for drug clearance.
What is the blood flow to the Liver? What is a drug that is metabolized extensively by the Liver.
90L/h (in an average 70kg person).
Morphine is also esclusivley metabolised by the liver and so its clearance is very rapid and approaches liver blood flow (60L/h).
Some drugs that are metabolized by the liver pass into the bile unchanged. Why does biliary excretion not necessarily mean biliary elimination?
Drug that passes into the bile could pass back into the blood by being reabsorbed in the small intestine.
What is the blood flow to the kidney? Why do most drugs not approach this clearance value?
70L/h (in an average 70kg person).
However most drugs are filtered through the glomerulus and the upper limit on renal clearance by glomerular filtration is the glomerular filtration rate of 6L/h (in an average 70kg person).
Some drugs such a Penicillin which are actively secreted by the tubules can have clearances approaching renal blood flow.
What is the difference between constant clearance, concentration dependent clearance and flow dependent clearance?
Constant/first order
Glomerular filtration clearance and the majority of drug clearance is considered constant which means it is unaffected by concentration or blood flow. Although clearance may be unchanged by concentration, elimination is still altered by concentration.
Concentration dependent/mixed order
The clearance of some drugs changes with changing concentration. Eg, penicillin which is eliminated via tubular secretion is a saturable process (the drug is moved via transporters and these transporters can all become occupied at high drug conc) and Phenytoin (an anticonvulsant medicine) can also saturate its metaboliser.
Flow dependent/
Changes in blood flow will affect clearance. This is primarily for drugs metabolised by the liver. For example morphine, if morphine is given to someone with heart failure then blood flow will be reduced to the liver and so morphine clearance is reduced and therefore maintenance dose should be reduced.
The concentration producing 50% of the maximum elimination (Vmax) is the Km. If the concentration of the drug given to the patient is small compared to Km then what type of elimination will occur?
First order. This means the rate of elimnation is linearly dependent on concentration.
If the durg conc is high compared to Km then it can be assumed to be a zero order reaction ( this does not occur in reality).
If the drug conc is neither small nor large in comparison to the Km then it is considered a mixed order reaction. This should be the general considered case for all drugs eliminated by metabolism.
What two equations is CL in that can help predict other drug dose measures?
Clearance can be used to predict maintenance dose.
MD = CL x target C
Clearance can also be used to calculate the half life of a drug in the body.
T1/2 = 0.7 x V / CL
What are some applications of clearance in terms of Theophylline?
Haemodialysis
Clearance can be measured and compared to normal expected values to see how well dialysis is substituing renal function.
Haemoperfusion
Where blood is passed through a cartridge which is designed to absorb the drug. Haemoperfusion can double the clearance of haemodialysis (9L/h).
Gut absorption
Charcoal in the gut can bind to/absorb drug thus preventing it from being reabsorbed. This can double theophylline clearance.
