Pharmacokinetics lecture 3 Contents . Compartments Bioavailability Salt factor. Compartments. T3. Compartment 1 Blood + tissues 1 & 2. Blood. T2. T1. Compartment 2 Tissues 3 & 4. T4. Compartments.
Blood + tissues 1 & 2
Tissues 3 & 4
All tissues penetrated rapidly or not at all.
Combine blood and all penetrated tissues (T1 & T2) as a single compartment.
Drug assumed to spread ‘instantly’ throughout all of this space.
Drug penetrates some tissues rapidly and others slowly.
Combine blood and rapid tissues (T1 & T2) as first compartment. Drug spreads ‘instantly’ through this compart-ment.
Combine slow tissues (T3 & T4) as second compartment.
2. Chemical, enzymatic
or bacterial attack
4. First pass metabolism
in gut wall or liver
3. Failure of
absorption & Pgp efflux
1. Failure of disintegration
Intestinal epithelium is rich in drug metabolising enzymes. Main Cyt P450 is CYP3A4
Cytochrome P450 activity in intestinal epithelium relative to liver (%)
Duodenum Ileum Colon
50 30 10 2
The drug administered may not be chemically identical to the drug measured in blood.
e.g. Phyllocontin tablets contain 225mg of aminophylline. But, target plasma conc. normally quoted as a theophylline conc.
Aminophylline contains approx. 80% theophylline by weight. S = 0.80
Predict initial plasma concentration of theophylline when 500 mg aminophylline injected i.v. into 70 kg adult. (V = 0.48 L/kg)
V = 0.48 L/kg x 70 kg
= 33.6 L
C = D x S = 500 mg x 0.80
V 33.6 L
= 11.9 mg/L
A drug is administered as a complex containing 75% (by weight) of the parent drug. The volume of distribution of the drug is 1.8 L/kg.
What dose of the complex would need to be administered (i.v) to a 90kg patient in order to achieve an initial plasma concentration of 15µg/L? The dose should be expressed in
units of mg.
V = 1.8L/Kg x 90Kg
= 162 Litres
V = D/C0
D = V x C0
= 162L x 15µg/L
= 3,240 µg
= 3.24 mg
of use of a salt
First pass metabolism