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BIOFARMASETIK

BIOAVAILABILITAS &
BIOEKIVALENSI (BA/BE)

NONI RAHAYU PUTRI, M.FARM,


APT

Sekolah Tinggi Ilmu Farmasi


OBJECTIVES OF BIOAVAILIBILITY STUDIES
• Primary stages of development of a suitable
dosage for a new drug entity.
• Development of a new formulations of the
existing drugs.
• Control of quality of a drug product during the
early stages of marketing in order to determine
the influence of processing factors, storage and
stability on drug absorption.
• Useful in determining the safety and efficacy of
the drug product.
Availabilitas Relatif
• Availabilitas relatif adalah ketersediaan sistemik
suatu produk obat dibandingkan terhadap suatu
standar yang diketahui.
[AUC]A / DOSIS A
Availabilitas relatif =
[AUC]B / DOSIS B

[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

• The difference between AB dan RBA is illustrated


by the following hypothetical example, assume
that:

• IV injection (product A)
• Oral dosage form No 1 (product B)
• Oral dosage form No 2 (product C)

• All containing the same dose of the same drug.


FAKTOR YANG MEMPENGARUHI
BIOAVAILABILITAS OBAT
FAKTOR YANG MEMPENGARUHI
BIOAVAILABILITAS OBAT

Sifat fisiko Dosage Waktu


Fisiologis
kimia obat Forms transit GI
1. IN-VIVO STUDIES

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.

MAXIMUM SAFE CONCENTRATION-


The plasma concentration of the drug beyond which
adverse effects are likely to happen.

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.

The AUC is independent of the route of


administration and processes of drug elimination as
long as the elimination processes do not change.
METHODS FOR ASSESSING BIOAVAILABILITY

2. Urinary drug excretion


Jumlah kumulatif obat yang dieksresi dalam urin
(Du)
Laju eksresi obat dalam urin (dDu/dt)
Waktu untuk terjadi eksresi obat max dalam urin
(t∞)
PARAMETERS OBTAINED FROM URINARY DRUG
EXCRETION STUDIES
• increases as the rate and
1. (dDu/dt )max /or extent of absorption
(maximum urinary increases.
excretion rate) • Analogous to Cmax derived
from plasma studies.
• decreases as the
2. (tu)max absorption rate increases.
(time for maximum • Analogous to t max
excretion rate) derived from plasma
studies.
3. Du: • increases as the extent of
absorption increases.
(cumulative amount • Related to AUC of plasma
of drug excreted in level data
urine)
METHODS FOR ASSESSING BIOAVAILABILITY
3. Efek farmakodinamik akut
Efek farmakodinamik maksimum (E max)
Waktu untuk mencapai efek farmakodinamik
max
Area bawah kurva efek farmakodinamik -
waktu
Mula kerja efek farmakodinamik
4. Pengamatan klinis
Uji klinis dengan kendali yang baik.
5. Studi In-Vitro
Drug dissolution.
BIOEQUIVALENT DRUG PRODUCTS:-

Two products are bioequivalent if :

– they are pharmaceutically equivalent


– both rate and extent after administration in
the same molar dose are similar to such a
degree that their effects can be expected to
be essentially the same.
...
• EXAMPLE:

• A 10 mg. tablet of Zocor (used to treat high


cholesterol) is therapeutically equivalent to a 10 mg.
tablet of simvastatin.

• A 50 mg. tablet of Zoloft (used to treat depression) is


therapeutically equivalent to a 50 mg. tablet of
sertraline.
THERAPEUTIC ALTERNATIVE

Drug products containing different active ingredients


that are indicated for the same therapeutic or clinical
objectives.

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???