Learning objectives

1
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.

2
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

3
Plasma concentration
-tKel
Ct Co e
lnCt lnCo - Kel t
logCt logCo - Kel . t
2.303
y c m x
4
Bioavailability
Plasma concentration
i.v. route
(AUC)o / (AUC)iv
oral route
Time (hours)
5
1.5 antilog 1.5 31.6
logCt logCo - Kel . t
2.303
TIME (hours)
log plasma concentration
6
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

7
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 (Ddose
  Tinterval 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

8
plasma conc
toxic
effective
Cumulation and use of loading doses
Time