Elimination

Question 1

Elimination

Answer 1

Irreversible elimination of drug from body by ALL routes.

Question 2

Elimination Routes (2)

Answer 2

1. Metabolism

2. Excretion

Question 3

Metabolism

Answer 3

• Chemically converting a drug to a metabolite
• AKA biotransformation
• Usually enzymatic which are usually found in liver
• Other tissues also have biotransformative enzymes (lungs, skin, kidneys, etc.)

Question 4

Excretion

Answer 4

• Removal of intact drugs
• Done primarily by kidney
• Other pathways include excretion into bile, sweat, milk, or other body fluids

Question 5

First Order Elimination Rate Constant (K)

Answer 5

• Proportionality constant relating rate and amount of drug eliminated
• Unit = time^(-1)
• Least-squared regression line is most accurate measurement
• Liver & kidney are the most important elimination organs

Question 6

K Equation

Answer 6

K = ke + km

t1/2 = 0.693 / K

(fe * K = ke, same for fm/km)

Question 7

Fraction excreted (fe)

Answer 7

Percent of drug excreted uncharged in urine

Question 8

Fraction metabolized (fm)

Answer 8

Percent of drug metabolized by body (ALL metabolites)

Question 9

Clearance

Answer 9

• Proportionality constant describing relationship between a drug’s rate of elimination at a given time and its corresponding fluid
• Measure of elimination without mechanism or process
• Considers entire body as a drug elimination system from which many processes occur
• Refers to Volume of Fluid Cleared / Unit Time
• Rate of removal varies as drug declines but clearance will be a constant since body fluid is a constant

Question 10

Clt equation

Answer 10

Clt = Clr + Clnr

Clt = Total Clearance
Clr = Renal Clearance
Clnr = Non-renal Clearance

Cl = VK
Cl = FDose / AUC ** Preferred method since doesn't depend on half lives or V**

Question 11

Physiological Approach to Clearance

Answer 11

• Models based on drug clearance through individual organs/tissue groups
• Based on mass balance concept
• Extraction ratio utilized

Question 12

Extraction Ratio (E)

Answer 12

E = (Ca - Cv) / Ca

Ca = arterial drug concentration
Cv = venous drug concentration
-Quantifies the organ efficiency with elimination and fixed flow
-Ranges from 0-100%
-E = 0 (none removed), E < 30% (not efficiently removed), E > 70% (efficiently removed)

Question 13

Clearance + Elimination Ratio

Answer 13

-For any organ, clearance may be defined as the fraction of blood volume containing drug that flows through an organ is elimination per unit time

Cl = QE

Q = Organ blood flow
E = Elimination ratio