FARMAKOKINET

IKA
Maya Dian Rakhmawatie, FK UNIMUS

The various phases of drug

action

Dos
e

I. Pharmaceutical phase
Disintegration of dosage form
Dissolution of active
substance

(Pharmaceutical
availability)

Drug available
for absorption

II. Pharmacokinetics phase

Absorption, distribution,
metabolisme,
excretion

Obje
ct
(Biologiva
Drug available
for action
Resu l
availabilit
III.
lt
y) Pharmacodynamic
Advanta phase
Effec
Drug-receptor interaction
t
ge

DEFINITION
Pharmacokinetics is
* the study of rate processes
involved in the absorption,
distribution, metabolism, and
excretion of drugs
* their relationship to the
pharmacological, therapeutic, or
toxic response in animal or humans

MEANING
1. Subject of kinetics
concerned the relationship
between the movement of a
drug through the body and the
processes affecting it.

What the body does to the

drug?
Not
What the drug does to the
body?

2. It is a discipline which
describes the time-course of
the movement of a drug into,
around, and out of the body
(fate of drug in the body).

INTO
Absorption

AROUND
Distribution

D
Central

Central
Peripheral

OUT
Elimination

Central
Peripheral

Pharmacokinetic parameters
rates constant (How fast?)
transferable concentration (How much?)

3.The uses of pharmacokinetic

knowledge are to describe, predict
and control the pharmacological,
therapeutic and toxic response of a
drug
(describe what happens?).
Pharmacokinetics should use words
beside symbols and mathematical
equations to express and predict
drug behavior.

4.There are two important basic

concepts
(i.e. order kinetics and
compartment model)
for describing the fate of drug in
the body.

PROCESS OF THE STUDY

Dose (IV or EV)

Subject/
Biological
System

Sampling
Assay
Plotting concentration vs
time Calculating
parameters
Analysis &
Evaluation

Applicatio
n

NOTATIONS and THE MEANING in

PHARMACOKINETICS

CONCENTRATION
C concentration
C0 at time 0
Ct at any certain time
Cmax maximum concentration
Cmin minimum concentration
Css concentration at steady state

NOTATIONS and THE MEANING in

PHARMACOKINETICS

VOLUME DISTRIBUTION

Vd Volume distribution
Vd Dose
Co
Influenced the amount of body fluid
(hydrophilic / hydrophobic), drug binding
to proteins

NOTATIONS and THE MEANING in

PHARMACOKINETICS

T ELIMINATION

Time needed for drug levels in the blood

is reduced to half its original level
Short t < 3 hour
Medium t 3 6 h
Long t 8 14 h
Very long t > 14 h

NOTATIONS and THE MEANING in

PHARMACOKINETICS

AREA UNDER CURVE

(AUC)

AUC Model (Compartment Model) Co/k

AUC Non Model (Trapezoid) describes
the drug levels physiologically

NOTATIONS and THE MEANING in

PHARMACOKINETICS

CLEARANCE (CL)

A parameter elimination, clearance of

drugs from the body fluid per unit time
Elimination of a drug changes according
to the levels of the drug in the body

JOURNEY FROM THE PLACE OF DELIVERY OF

THE DRUG, THE ACHIEVEMENT OF THE
CIRCULATORY SYSTEM UNTIL THE ONSET OF
EFFECT
Per
Oral

Mouth
Gastric

Lymphat
ic

Intestine
Intestinal Flora
Intestinal Wall
liver
Lungs
Central Compartment
Periphery Compartment

Rectal

Bile

Intra
Peritoneal
Iv, im, sc,
buccal
inhalatio
n
eliminatio
n
Effect

PLACE OF PHARMACOKINETICS
IN OTHER SPECIALITIES

Biophamaceutics
Pharmacogenetics

TDM

Practical
therapeutics

Targeting of
Drugs
First Past effect

Pharmacokinetics

Drug delivery
technology

Chronopharmacokinetics

COMPARTEMENT MODELS
Simplify the structure of the body (animal or
human) complex into a simple mathematical
model to explain the concept of ADME
Compartment Models
a. 1-compartment
b. 2-compartment

Non Compartment Models/

Physiology Models
To
link
the
relationship
between dose, drug levels,
and drug disposition in the
body tissues

2-compartment models

1-compartment models

Piotrowski,
JK.
1977.
Retention
and
Excretion Kinetics of Chemical Agents.
Wiley Online Library

NARROW THERAPEUTIC
RANGE
DRUG

DISEASE/CONDITIO
N

THERAPEUTIC
RANGE (mg/L)

Salicylic acid

Rheumatic fever

250 400

Valproic acid

Epilepsy

40 100

Gentamycin

Antibiotic

4 12

Digoxin

Cardiac Dysfunction

0,01 0,02

Warfarin

Thromboembolism

1- 4

Amitriptyline

Depression

0,12 0,25

Dipiro et al, 2005 ; Rowland and Tozer, 2005

Orde Reactions
Orde-0
Any number of drugs, its elimination rate remains
Orde-1
Drug elimination velocity proportional to the
amount of drug remaining

REFFERENCES
1. Atlas of Pharmacology
2. Hakim, L. 2011. Farmakokinetik.
Yogyakarta: Bursa Ilmu
3. Another Pharmacology Handbooks