Elimination and Clearance Flashcards
What is drug elimination?
Irreversible removal of drug from the body by all routes of elimination.
What is excretion?
Removal of intact drug.
What is biotransformation or drug metabolism?
Drug is chemically converted in the body to a metabolite.
What are the two major drug elimination organs in the body?
Kidney and liver
How are drugs excreted?
Bile, Urine, Sweat, Breast Milk, Exhaled Air
What is clearance?
Process of drug elimination from the body or from a single organ without identifying the individual processes involved.
Volume of fluid cleared of drug from the body per unit time.
The proportionality factor that relates rate of drug elimination to the plasma drug concentration.
The loss of drug across an organ of elimination.
What is the clearance equation?
Rate of elimination = Cl x Cp
Cp is plasma concentration
Will clearance change?
no
Will rate of elimination change?
yes
What is the equation for fraction of drug excreted?
fe = (Du/FD0) = (ke/k)
fe is fraction excreted
Du is amount of drug cumulative in the urine
F is bioavailability(assumed to be 1 in IV)
D0 is initial dose
ke is rate constant for excretion
k is rate constant efor elimination
What is the equation for renal clearance?
ClR = (Du/FD0)ClT = (ke/k)ClT = feClT
What is the equation for total body clearance?
ClT = ClR + ClH
Total clearance can be determined from what?
total exposure (AUC, area under the curve) following an IV dose. ClT = (D0/AUC)
Renal clearance can be determined how?
From the fraction excreted unchanged and total clearance.
ClR = fe x ClT
How is hepatic clearance measured?
Rate and extent of metabolism can rarely be measured directly, but by taking advantage of the additivity of clearance, hepatic clearance is readily estimated as the difference between total and renal clearance.
ClH = (1 - fe) x Cl
ClR = ClT - (feClT)
Appearance of drug in the urine is the net result of?
filtration, secretion, and reabsorption.
What are the three mechanisms of renal excretion?
Glomerular filtration- passive diffusion of drug across the glomerulus
Tubular secretion -active secretion of some drugs from the blood into the urine.
Tubular reabsorption - reabsorption of some drugs form the urine back into the blood.
What is the max glomerular filtration that can occur?
130 mL/min
What is creatinine?
Creatinine is an endogenously produced compound that is neither bound to plasma proteins nor secreted and the entire filtered load is excreted into the urine. The renal clearance of creatinine is a estimation of GFR. It is the most common measure of renal clearance.
Where does creatinine clearance come from?
muscle breakdown.
Creatinine clearance can be calculated by what?
The Cockcroft-Gault equation with 120-130 mL/min being considered normal.
CrCl = (140-age)(IBW) / (72 x SCr) ( x 0.85 if female)
assuming woman have 15 % less muscle
age in years, IBW in kg
male IBW = 50 +2.3(inches over 5 ft)
female IBW = 45.5 + 2.3(inches over 5 ft)
SCr = serum creatinine in mg/dL
What is active secretion?
Secretion is inferred when rate of excretion exceeds the rate of filtration. Secretion is apparent when renal clearance is greater than the GFR.
What is tubular reabsorption?
Reabsorption occurs if the renal clearance is less than the calculated clearance by filtration.
What are the two major components of drug elimination from the body?
Excretion and biotransformation.
