Learning objectives

• To know what data is available from pharmacokinetic

studies in man and how to handle it
• To know how to calculate the basic pharmacokinetic
parameters of clearance, t(half); volume of distribution,
bioavailability; Kel
• To understand the implications of these parameters for
satisfactory therapy and the construction of suitable
dosage regimens for patients
• To know how knowledge of pharmacokinetic parameters
can be exploited in drug design and formulation
development.
 Pharmacokinetics
• Study of ADME on a quantitative basis
In man study blood, urine, faeces, expired air.
Measure urine volume & concentration of drug
conc in urine x vol per min = RENAL
plasma concentration CLEARANCE
If neither secreted nor reabsorbed then clearance =
clearance of inulin = 120 ml/min
If completely cleared by secretion then clearance =
clearance of p-hippuric acid = renal blood flow = 700
ml/min
Plasma concentration
14 -tKel
Ct = Co e
12
10 lnCt = lnCo - Kel t
8 logCt = logCo - Kel . t
6 2.303
y = c m x
4
2
0
0 5 10 15 20
TIME (hours)
Plasma concentration
60
Bioavailability
50 i.v. route
(AUC)o / (AUC)iv
40

30 oral route
20

10 Time (hours)

0
0 2 4 6 8
1.6 =1.5; antilog 1.5 = 31.6
logCt = logCo - Kel . t
1.1 2.303

0.6

0.1 TIME (hours)

0 5 10 15 20
-0.4
log plasma
-0.9 concentration
 Pharmacokinetic parameters

• Volume of distribution V = DOSE / Co

• Plasma clearance Cl = Kel .V

• plasma half-life (t1/2) directly from graph

or t1/2 = 0.693 / Kel

• Bioavailability (AUC)x / (AUC)iv

 Multiple dosing

• On multiple dosing plasma concentration will rise and

fall with each dose andwill increase until
administration = elimination
ie. steady state is reached.
• At steady state hourly dose rate (D=dose; T=interval
between doses in hours)
D/T = clearance x plasma conc
or steady state conc = D/(T x clearance)
• At each dose the level will oscillate through D/V
plasma conc toxic
6

4
effective

3 Cumulation and use of

2
loading doses

1
Time
0
0 5 10 15 20 25