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
Blood drainage from G.I.T.
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