DDElimination1

Question 1

Does most elimination follow 1st order kinetics? What does this mean?

Answer 1

Yes (hepatic metablism and renal excretion are 1st order processes). Rate of elimination is proportional to concentration of drug in plasma (note this is RATE and not absolute amount - T to go from 8 units to 4 units = T to go from 4 units to 2 units. Half-life time is the same but rate is different)

Question 2

Does taking antibiotic increase or decrease your likelihood of becoming pregnant if you are on an oral antibiotic? Why?

Answer 2

It increases it. If the antibiotic kills the bacteria that normally do enterohepatic recycling then less drug gets reabsorbed and more gets excreted (I think). I think this is only in theory it is not actually clinically significant (unless the antibiotic is rifampin)

Question 3

Half-life

Answer 3

Characteristic of 1st order elimination kinetics. Constant fraction of drug is eliminated per time (time required to eliminate 1/2 of drug amount). Independent of total amount of drug present.

Question 4

Amount of half-lives it takes for a drug to be eliminated

Answer 4

4-5 half lives

Question 5

Time it takes to reach steady state (when drugs are administered continuously)

Answer 5

4-5 half lives

Question 6

Degree of fluctuations in plasma levels between doses

Answer 6

Number of half-lives in dosing interval

Question 7

What is half-life dependent on?

Answer 7

Dependent on clearance and volume of distribution. Inversely proportional to clearance and directly proportional to volume of distribution

Question 8

Clearance

Answer 8

CL = Vd x ke. Volume of plasma (Vd) which is completely cleared of drug in a given period of time by combined tissue processes (such as kidney excretion and liver (drug metabolism) et al.)

Question 9

Relationship between clearance; plasma concentration at SS and maintenance dose

Answer 9

Maintenance Dose/tau = CL x Cp(ss) OR CL = (Maintence Dose/tau)/(Cp(ss))

Question 10

Relationship between half-life and Ke

Answer 10

Ke is fraction of drug leaving body per unit time via all elimination processes. T1/2 = 0.693/ke

Question 11

Effects of blood flow on Hepatic clearance

Answer 11

Depends on how efficient metabolism is on that drug. If it is a low extraction drug (not efficiently metabolized) blood flow will not significantly influence clearance. If a high extraction drug then hepatic blood flow will have a major influence on clearance - all subject to coadministration of inhibitors/inducers

Question 12

Kidney function and renal clearance

Answer 12

Changes in renal function will alter clearance of renally eliminated drugs. Necessitates dose changes to prevent drug accumulation (renal dosing)

Question 13

Fold fluctuation

Answer 13

Fluctuation = 2 ^ x (x = number of half-lives in dosing interval)

Question 14

Effect of dosing interval on Cp(ss) Fluctuation

Answer 14

Bottom line is more half-lives (NOT more hours) in a dosage interval mean greater fluctuation. Amount of fluctuation in Cp that can be tolerated is determined by its “Therapeutic Index”