Pharmacokinetics

Question 1

Defintions: F, Cl, Vd

Answer 1

F=bioavailability
Cl=Clearance
Vd=volume of distribution

Question 2

Sketch zero order and first order kinetics. What does it mean

Answer 2

ref. notes. most drugs are first order=no accumulation, zero orderaccumulation e.g.alcohol, phenytoin. Zero order occurs in overdose

Question 3

What are zero order and first order kinetics determined on

Answer 3

zero order=same rate regardless [drug] dA/dt=-k

first order=rate dependent on k and [drug] dA/dt=-kA

Question 4

How 1 and 2 compartments differ, sketch graph

Answer 4

1=kinetically homogenous instantaneous distribution, monophasic decline in plasma [A] multi compartmental models can occur
2=central and peripheral compartment, equilibrium, biphasic decline ref. notes

Question 5

t1/2 define

Answer 5

time taken for plasma [A] to fall by half

Question 6

For first order kinetics, what does A= and plot ln[A] against time

Answer 6

dA/dt=kA
A=A0exp(-kt)
A=amount of drug, A0=initial amount of drug (y intercept), k=elimination rate constant (slope) ref. notes

Question 7

absorption what quantified by, what dependent on

Answer 7

quantified by absorption rate constant, dependent on solubility (dissolution rate) and pH (pKa). Solubility also dependent on pH

Question 8

Volume of distribution equation

Answer 8

Vd=total amount of drug dosed/plasma conc at tc

Question 9

Purpose of oxidation and conjugation in metabolism

Answer 9

oxidation=to make water soluble->conjugation (body conjugates water soluble conjugating group onto the drug to make entire new drug more soluble and more readily excreted from body

Question 10

What is clearance, what is it limited by and what is its equation

Answer 10

Clearance=volume of plasma cleared of drug per unit time
can be limited by organ blood flow, includes metabolism and excretion.
Cltotal=Clhepatic+Clrenal+Clmetabolic

Question 11

How to work out extraction ratio and clearance using human liver blood flow and Eh

Answer 11

Eh=(mg/ml of drug in-out)/(mg/ml drug in)

Clearance=Q*Eh

Question 12

What is max hepatic clearance

Answer 12

liver blood flow

Question 13

What happens to Eh and bioavailability as Cl tends to Q

Answer 13

Because Cl=Q*Eh, Eh tends to 1.

F=1-Eh so F tends to 0

Question 14

What is bioavailability, what is it for intravenous and oral dosing

Answer 14

F=fraction of unchanged drug reaching systemic circulation
IV=100%
Oral=limited by absorption from gut and gut/hepatic metabolism/excretion. Derived empirically from dose-adjusted AUC oral/AUCiv=F

Question 15

What is AUC of

Answer 15

area under curve of plasma conc x time graph

Question 16

List equations for relationship between t1/2 and k, Vd, Cl, F

Answer 16

1/2=0.693/k NB 0.693=ln2
Vd=DoseA/A0
Cl=k*Vd
Cl=dose/AUC
F=AUCoral/AUCiv

Question 17

sketch graphs to represent pharmacokinetics, pharmacodynamincs, PK/PD relationships

Answer 17

ref. notes