BIOAVAILABILITAS &
BIOEKIVALENSI (BA/BE)
[DU]∞A
% Availabilitas relatif = X 100
[DU]∞B
[DU]∞ : Jumlah total obat yang dieksresikan dalam urin
Availabilitas Absolut
• Availabilitas absolut obat adalah ketersediaan
sistemik suatu obat setelah pemakaian
ektravaskular (misal: oral, rektal, transdermal,
subkutan) dibandingkan dengan dosis I.V
Availabilitas Absolut
Availabilitas absolut setelah pemberian oral
menggunakan data plasma dapat dirumuskan:
[AUC]PO / DOSISPO
Availabilitas Absolut = F =
[AUC]IV / DOSISIV
Availabilitas
Absolute availabilityabsolut menggunakan
using urinary drug excretion data data
can be eksresi
determinedobat
by the
following: dalam urin dapat ditentukan dengan:
[DU]∞PO / DOSISPO
Availabilitas Absolut =
[DU]∞IV / DOSISIV
DIFFERENCE BETWEEN ABSOLUTE AND RELATIVE BA
• IV injection (product A)
• Oral dosage form No 1 (product B)
• Oral dosage form No 2 (product C)
Pharmacokinetic Pharmacodynamic
(Indirect ) (Direct )
1. Acute
1. Plasma level
pharmacological
time studies
response
2. Urinary
2. Therapeutic
excretion
response
studies
2. IN-VITRO STUDIES
METHODS FOR ASSESSING BIOAVAILABILITY
Parameters :
1. Plasma drug concentration
Waktu konsentrasi plasma (darah) mencapai
puncak (t max)
Konsentrasi plasma puncak (C max)
Area dibawah kurva kadar obat dalam plasma
(darah) (AUC)
PARAMETERS OBTAINED FROM
PLASMA LEVEL DATA
1. TIME FOR PEAK • Rate of drug
PLASMA absorption
CONCENTRATION
(TMAX)
2. PEAK PLASMA
DRUG
CONCENTRATION • Rate & Extent
(CMAX)
3. AREA UNDER
PLASMA DRUG • Extent of drug
CONCENTRATION- absorption
TIME CURVE (AUC)
24
Plasma concentration time profile:-
MINIMUM EFFECTIVE CONCENTRATION-
The minimum plasma concentration of the drug required to
achieve a given pharmacological or therapeutic response.
This value varies from drug to drug and from individual to
individual as well as with the type and severity of the
disease.
THERAPEUTIC RANGE-
The range of plasma drug concentration in which the
desired response is achieved yet avoiding adverse effect.
The aim is clinical practice is to maintain plasma drug
concentration within the therapeutic range.
ONSET OF ACTION-
The beginning of pharmacological response.
On set of action is the time required to achieve the
minimum effective plasma concentration following
administration of drug formulation.
DURATION OF ACTION-
Duration of action of the therapeutic effect of the drug is
defined as the time period during which the plasma
concentration of the drug exceeds the minimum effective
level.
INTENSITY OF ACTION-
It is the maximum pharmacological response produced by
the peak concentration of drug.
AUC (AREA UNDER CURVE)
• The AUC reflects the total amount of active drug
that reaches the systemic circulation.
where :
F : fraction of dose absorbed,
D0 : dose,
k : elimination rate constant,
VD : volume of distribution.
For example:
Cimetidine may be given instead of Rantidine
PHARMACEUTICAL EQUIVALENTS:
FDA considers drug products to be pharmaceutical
equivalents if they meet these criterion:
• Shape
• Active • Labeling
ingredients • Release
• Dosage form DIFFE mechanism
SAME • Route of RENT • Scoring
administration configuration
• Strength/ • Excipient
Concentration
GENERIC OR BRAND-NAME DRUG???