FARMAKOKINETIKA

KLINIK
RISHA FILLAH F, MSc., Apt
 FARMAKOKINETIKA
 ilmu yang mempelajari kinetika absorpsi,
distribusi dan eliminasi (yakni, ekskresi
dan metabolisme) obat,berdasarkan kadar
obat yg terukur dalam cairan tubuh vs
waktu pemberian.
 Perubahan yang dilakukan oleh tubuh
terhadap obat
Gambaran skematik peristiwa absorpsi, metabolisme, dan
ekskresi dari obat-obat setelah berbagai rute pemberian.
 intensitas
efek farmakologi  tergantung
pada kadar/jumlah obat dalam tubuh

Rentang kadar kerja efektif obat

(therapeutic window) dapat ditentukan.
PROFIL FARMAKOKINETIKA
 PARAMETER DASAR
FARMAKOKINETIKA
 Tetapan kecepatan absorbsi (ka)
 Menggambarkan kecepatan absorbsi
 Satuan fraksi persatuan waktu (jam-1 atau
menit-1)
 Waktu mencapai kadar puncak (Tmax)
 Menunjukkan kecepatan absorbsi
 Satuan : jam atau menit
 Kadar puncak (Cmax)
 Menggambarkan derajad absorbsi, tolok ukur
toksisitas
 Satuan berat/volume (mg/ml)

 Tetapan kecepatan eliminasi (Kel)

 Menunjukkan laju penurunan kadar obat
 Satuannya fraksi per waktu (jam-1 atau menit-1)

 Waktu paro eliminasi (t1/2)

 Waktu yang diperlukan agar kadar obat dalam
darah berkurang separonya
 T1/2 = 0,693/Kel
 Luas daerah di bawah kurva kadar obat
dalam sirkulasi sistemik vs waktu (AUC)
 menggambarkan derajad absorbsi yaitu
seberapa banyak obat diabsorbsi
FARMAKOKINETIKA
KLINIK ????
MENGAPA ???

DIAGNOSIS
AKURAT

PENGETAHUAN OBAT TERAPI

KONDISI KLINIS TEPAT OPTIMAL
PASIEN

PENGUASAAN
FARMAKOTERAPI
 PENGGUNAAN OBAT
 BERAPA BANYAK ???  DOSIS
 BERAPA SERING ???  FREKUENSI
 BERAPA LAMA ???  RESIKO
TOKSISITAS, ESO

TERJAWAB DENGAN PENELITIAN

FARMAKOKINETIK
 FARMAKOKINETIKA KLINIK
 PENERAPAN FARMAKOKINETIKA DALAM
PENGOBATAN PASIEN (KLINIK)

 MEMANTAU/MENYESUAIKAN
PENGGUNAAN OBAT  RESPON
OPTIMAL/RESIKO MINIMAL
 FARMAKOKINETIKA KLINIK
 Farmakokinetika yang diterapkan di klinik
 Studi yang mempelajari tentang ADME
suatu obat baik pada orang sakit maupun
orang sehat
 TUJUAN
 Mengetahui nasib obat (ADME) di dalam
tubuh manusia sehat dan sakit
 Mengetahui perubahan ADME obat pada
individu yang sedang sakit
 Menetapkan Regiment Dose yaitu berapa
besar dosis dan frekuensi pemberian obat
baik dalam membantu dokter di RS
maupun R&D di Industri
 MANFAAT
 Membantu dalam pemilihan obat
 Membantu dalam penetapan dosis
 Menerangkan fenomena gejala ketoksikan
ataupun keadaan pengobatan subterapi
 Menerangkan fenomena terjadinya
interaksi obat
 VARIABEL YANG MEMPENGARUHI
ADME SUATU OBAT

Obat subjek farmakokinetika (ADME) efek

farmakodinamika (ikatan dg reseptor)

1. enzim pemetabolisme
2. hormon faktor
3. organ faal (jantung, hati, ginjal, GI) hayati/
4. mineral faal
5. aliran darah
 FAKTOR INTERNAL
 Usia
 Berat badan
 Genetik/ras
 Penyakit
 Jenis kelamin
 FAKTOR EKSTERNAL
 Obat
 Makanan
 Minuman
 Senyawa asing
 Ketinggian tempat
 Faktor diurnal
 APPLICATION OF
PHARMACOKINETICS IN
CLINICAL SITUATIONS
 The succes of drug therapy is highly
dependent on the dosage regimen design.

 A properly designed dosage regimen tries

to achieve an optimum concentration of
the drug at a receptor site to produces an
optimal therapeutic response with
minimum adverse effects.
 Individual variation in pharmacokinetics
and pharmacodynamics makes the design
of dosage regimens difficult

 Individualization of drug dosage regimen

 Not all drugs need rigid individualization of the
dosage regimen

 Wide therapeutic window  a broad safety dose

range : penicillins, chepalosporins & tetracyclines
; ibuprofen, cimetidine, naproxen, nichotin
pathces
 Narrow therapeutic window individualization of
dosage regimen is very important : digoxin,
aminoglycosides, antiarrhythmics,
anticonvulsants, theophylline
 The monitoring of plasma drug
consentrations is valuable only if there is a
relationship between the plasma drug
consentration & the desired clinical effect
or between drug concentration and an
adverse effect

 If those are not related, other

pharmacodynamic parameters may be
monitored.
 Therapeutic range for a drug is an
approximation of the average plasma drug
concentrations that are safe & efficacious
in most patients

 Realize : More a probability concept &

should never be considered as absolute
values
 Therapeutic Range for Commonly
Monitored Drugs

 Amikacin 20-30 mcg/mL

 Carbamazepine 4-12 mcg/mL
 Digoxin 1-2 ng/mL
 Gentamicin 5-10 mcg/mL
 Lidocaine 1-5 mcg/mL
 Lithium 0.6-1.2 mEq/L
 Phenytoin 10-20 mcg/mL
 Procainamide 4-10 mcg/Ml
 Quinidine 1-4 mcg/mL
 Theophylline 10-20 mcg/mL
 Tobramycin 5-10 mcg/mL
 Valproic acid 50-100 mcg/mL
 Vancomycin 20-40 mcg/mL
 Various pharmacokinetic methods may be
used to calculate the initial dose or dosage
regimen.

 Initial dose or dosage regimen is

calculated based on :
 Body weight or body surface
 Pharmacokinetics of the drug
 The pathophysiologic condition of patient
 The patient’s drug history
 Due to interpatient variability in drug
absorption, distribution and elimination as
well as changing pathophysiologic
conditions in the patient

 Therapeutic drug monitoring (TDM) or

clinical pharmacokinetic (laboratory)
services
 The FUNCTION of a TDM services
 Select drug
 Design dosage regimen
 Evaluate patient response
 Determine need for measuring serum drug
concentrations
 Assay for drug
 Perform pharmacokinetic evaluation of drug levels
 Readjust dosage regimen
 Monitor serum drug concentrations
 Recommend special requirements
 Drug selection
 An important considerations in drug
selection
 The basis of therapeutic, cost & therapeutic
equivalency
 Pharmacokinetic & pharmacodynamics
 Patient specific information : medical history,
pathophysiologic states, concurrent drug
therapy, known allergies, drug sensitivity &
drug interaction
 Dosage Regimen Design
 A number of factors must be considered:
 The usual pharmacokinetics of drug : ADME profile
 Physiology of the patient: age, weight, gender &
nutritional status
 Pathophysiologic conditions : renal dysfunction,
hepatic disease, & congestive heart failure  may
change the normal pharmacokinetics profile of drug
 The hidden effect of exposure to longterm medication
or drug abuse
 Personal life style factors : cigarette smoking &
ethanol abuses  alter pharmacokinetics of drug
 The overall objective of dosage regimen is
to achieve a target drug consentration at
the receptor site.

 Alert to change the dosage or consider the

selection of another medication : change
in drug’s pharmacokinetics, drug
tolerance, cross sensitivity history of
unusual reaction to related drugs