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Pharmacokinetics
and bioavailability
study
Rustamaji
Department of Clinical Pharmacology
Faculty of Medicine
Gadjah Mada University
2008
Absorption
Distribution
Metabolism
Excretion
Pharmaco
kinetics
Pharmaco
dynamics
Therapeutic effect
Site(s) of action
Free Drug
Absorption
DrugProtein
Excretion
tes
i
l
o
ab
Met
Free Drug
Metabolism
Pharmacokinetics
A study of the quantification of drugs in the
body
Pharmacokinetics:
Minimum Toxic
Concentration
Tlag
Tmax
Minimum Effective
Concentration
Sub-therapeutic
concentrations
Time
Preclinical pharmacokinetics
Etc.
Clinical pharmacokinetics
Age, sex
Meals
Liver/kidney dysfunction
Obesity
Etc.
Widely known as
bioavailability
Pharmacokinetic study
laboratory findings
Pharmacokinetic analysis:
single or multi-compartments?
manual or computerized?
Statistical analysis:
Anava + paired T-test
Confidence interval analysis
Bioequivalence studies
Types of BE studies
Pharmacodynamic studies
Clinical trials
Considerations:
When the drugs produce meaningful concentration in
plasma, bioavailability study is preferred
When drug concentration is not measurable, bioefficacy
study is preferred
Justification for
bioequivalence
Multiple dosing?
60
50
40
30
20
10
0
10
12
60
50
40
30
20
10
0
10
12
Justification for
bioequivalence
multiple dosing
First dose:
Rate of bioavailability (T
lag & Tmax)
Extent of bioavailability (C
max & AUC0-)
Evidence of adverse events
At steady state 5th-6th dose):
Rate of bioavailability (T
max)
Extent of bioavailability (C
min, Cmax & AUC0-t)
Fluctuation
Evidence of adverse events
Drug concentration vs time curves
Cmax and Cmin within therapeutic window
A
R
Pharmacokinetic analysis:
single or multi-compartments?
manual or computerized?
Statistical analysis:
Anova + paired T-test
Confidence interval analysis
80-125%
Comparator
Bio-Creep
Interchangeable
Not Interchangeable
Developing
a slow-release diclofenac formulation
Plasma concentration
(ng/mL)
MEC = 20 ng/mL
Hour
Suryawati, 1989
Theophylline 1x daily
Plasma concentration (ug/mL)
15
1
0
24
48
72
96
120
144
Hours
Suryawati, 1999
Approval of copy/generic
products
Plasma nifedipine concentration (ng/ml)
Time (hours)
Rifampicin
in combination with other anti-TBs, multiple dosing
Time (hours)
Suryawati, 1994
Time (hours)
Suryawati, 1992
Captopril tablets 25 mg
Plasma concentration (ng/mL)
Time (hours)