Pharmacokinetics of Elimination

Question 1

Define Clearance (CL):  
1.

Answer 1

• Selecting maintenance dose, dosage adjustments necessitated by alteration of kidney or liver function.
• the volume of plasma which is completely cleared of drug in a given period of time by the processes of kidney excretion and drug metabolism (with some contribution from other tissues).

Question 2

Ke is:

Answer 2

• fraction of drug eliminated per unit time
• number or constant that allows us to calculate the amount of drug remaining at any time during the elimination process.

Question 3

Clearance = (equation)

Answer 3

volume of distribution (Vd) x Ke

Question 4

Clearance: proportionality constant that makes the average plasma concentration at steady state equal to the _______

Answer 4

-rate of administration

Question 5

Maintenance dose/tau= (equation)

Answer 5

CL x Cp(ss)

Question 6

Half-life (t1/2):

Answer 6

Time to steady state or removal from body, selecting dosage intervals, relation to fluctuations in plasma drug levels between drug doses (difference between Cp max and Cp min).
-The time required to eliminate ½ of the drug amount present in the body
-

Question 7

Drug with T1/2 of 3 hours, takes 3 hours for drug concentration to go from 1000 mg/ml to ______ mg/ml and another 3 hours from drug to go to _______` mg/ml.

Answer 7

• 500

- 250

Question 8

Time it takes for drug to be essentially eliminated (______ half-lives)

Answer 8

4-5

Question 9

Time it takes to reach steady state when drugs administered continuously (_______ half-lives)

Answer 9

4-5

Question 10

Degree of fluctuation between doses=

Answer 10

2x, where x=# of t1/2 in T

Question 11

t1/2 = (equation)

Answer 11

0.693/ke

Question 12

First-order: Implications for chronic dosing regimens

Answer 12

-Virtually all drugs eliminated via first-order kinetics which means the rate of elimination (mg/hr) is proportional to the concentration of drug in the plasma (mg/L)
(If concentration of drug is doubled the rate of elimination is doubled)
-As drug is eliminated from the body, its concentration is CONSTANTLY CHANGING, therefore rate of elimination also changes constantly
-CONSTANT FRACTION of drug is eliminated per time and this is INDEPENDENT OF THE TOTAL AMOUNT OF DRUG PRESENT
-Most clinically used drugs are eliminated by first-order kinetics when given in doses within the therapeutic dosage range because the major biological processes responsible for drug elimination, hepatic metabolism and renal excretion, are first-order processes.

Question 13

Zero-order kinetics: Implications for chronic dosing regimens

Answer 13

• Process in which the rate of elimination of drug from the body is INDEPENDENT of the amount of drug in the body. The amount of drug removed per unit time is constant.
• Most often occurs due to saturation of hepatic metabolic enzyme systems by drug administration. This enzyme saturation occurs with therapeutic doses for only a FEW drugs (aspirin, phenytoin, EtOH) and with toxic doses for most hepatically eliminated drugs. Drugs eliminated by zero-order kinetics don’t have half-lives, can present dose adjustment challenges especially at the upper end of the therapeutic range of narrow therapeutic index drugs, where a small change in dose can produce large changes in plasma concentrations and subsequent toxicity.