THERAPEUTIC DRUG

MONITORING (TDM)
AMINAH DALIMUNTHE 1

Farmasi Klinis
 Polifarmasi

Profil
Gangguan fx
Farmakokin
ginjal/hati
etika

Dosis
individual

Therapeutik Drug Monitoring

Farmasi Klinis 2
 Obat

Konsentrasi Obat dalam Darah

Konsentrasi Obat pada Side of Action

Efek
Farmasi Klinis 3
Obat-obat yang tidak perlu di TDM kan

1 Obat yang memiliki titik akhir klinis jelas, cth :

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●

TD, KGD, TG, HDL,LDL, Suhu, nyeri

2 Efek terapi/toksik tidak tergantung pd

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●

konsentrasi obat dlm serum

3 Obat yang sifat farmakokinetiknya umum (less

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●

complicated)

4 Obat yang digunakan untuk penyakit non komplikasi

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●

atau yang membahayakan kehidupan pasien

Farmasi Klinis 4
JENIS OBAT YANG DI-TDM-KAN

1 Bronkodilator Teofilin

2 Antibiotik Aminoglikosida, Vankomisin

3 Imunosupresan Siklosforin

4 Antikanker Metotreksat
JENIS OBAT YANG DI-TDM-KAN
Phenobarbital, Phenytoin,
5 Antiepilepsi Carbamazepine, Valproate

6 Obat Jantung Digoksin,

7 Obat Psikoaktif Litium

8 Analgetik Parasetamol, Aspirin

 KRITERIA TDM

Tersedia metode pengukuran

Indeks terapi sempit

Tidak ada hub dosis-SDC (serum drug concentrations)

Ada hub SDC-efek terapi/toksik

Sifat farmakokinetika non-linier

Farmasi Klinis 7
 KRITERIA TDM

Berbahaya jika terjadi kegagalan terapi

Sulit menandai gejala toksisitas atau kegagalan suatu terapi

Farmasi Klinis 8
 TDM ASSAY METHODOLOGIES

Jenis Kelebihan Kekurangan

EMIT highly automated, poor stability of
rapid turnaround, calibration curve
many assays available,
homogenous,
moderate sensitivity
ELISA Highly automated, few assays available,
rapid turnaround, heterogenous
moderate sensitivity
RIA high sensitivity long turnaround,
many interferences,
heterogenous,
radiation hazards

Farmasi Klinis 9
 TDM ASSAY METHODOLOGIES

Jenis Kelebihan Kekurangan

FPIA highly automated, -
rapid turnaround,
many assays available,
stability of reagents
and calibration curves,
moderate sensitivity,
homogenous

HPLC highest sensitivity, least expensive long

most assays turnaround,
availablety requires highly trained
personnel

Farmasi Klinis 10
 TDM

Metabolit

Total
Konsentrasi
konsentrasi
obat bebas obat

Farmasi Klinis 11
1 ●
Maksimal efikasi , Loading dose

2 ●
Minimalisasi toksisitas

3 Memperjelas sejarah penggunaan obat pasien

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4 Ada perubahan fungsi hati atau ginjal

●

MANFAAT TDM
Farmasi Klinis 12
5 ●
Ada interaksi obat

6 ●
Penyesuaian dosis individual

7 Menentukan terapi yang tepat atau selanjutnya

●

8 ●
Profil farmakokinetika

9 ●
Gejala toksisitas obat

Farmasi Klinis 13
FAKTOR YANG MEMPENGARUHI SDC

1. Disease states: renal, liver, cardiac, thyroid

2. Habits: diet, smoking, drinking
3. Pregnancy, age, weight
4. Non-compliance
5. Electrolyte balance : Digoxin vs K+ & Ca++
6. Drug interactions
7. Plasma protein binding
8. Bioavailability
9. Sampling time

Farmasi Klinis 14
 SAMPLING TIME
Complete
Complete
Steady state
absorpsion and
absorpsion state
Steady
distributionand
distribution

P
u
n
c
a
k
-
le
m
b
a
h
S
D
C

Farmasi Klinis 15
 Rate in = Rate out
Steady state
4-5 kali waktu paruh

Farmasi Klinis 16
Aminoglikosida
Toksisitas : Kegagalan
puncak & lembah terapi/Ketidakpatu
SDC han :puncak SDC

Farmasi Klinis 17
Memaksimalkan ●
Luka bakar-Gentamisin
Asma-teofilin
efikasi
●

Minimalisasi ●

●
Overdose
Perubahan farmakokinetika

toksisitas Interaksi obat

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Identifikasi ●

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Ketidakpatuhan
Dosis subterapi
Malabsorpsi

kegagalan terapi Interaksi obat

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Penyesuaian ●
New dose = Old dose X Desired Css/Old Css
dosis

MANFAAT KLINIS TDM

Farmasi Klinis 18
 COST-BENIFITS OF TDM
• HOSPITAL
- Reduce hospital congestion
- Increase quality of Rx and service
- Economic consideration
- Personnel: research, promotion & self
esteem
- Medico-legal aspects
• PATIENT CARE
- Decrease duration of stay in hospital
- Receive safer and more effective Rx
- More economic
- Increased productivity
- Improve quality of life

Farmasi Klinis 20
COST-EFFECTIVENESS OF METHODOLOGY
• Economic consideration
: Building cost
: Maintenance costs of equipment
: Equipment depreciation costs
: Medical supplies
: Salaries
DRUG TIME TO STEADY STATE SAMPLING TIME THERAPEUTIC RANGE
(MG/L)
AMINOGLYCOSIDES
AMIKACIN ADULTS
(< 30 Y): ~ 2.5-15 H PEAK 0.5-1 H AFTER IV INFUSION PEAK 15-25,
TROUGH< 5
KANAMYCIN (> 30 Y): ~ 7.5-75 H (1 H AFTER IM)
GENTAMICIN CHILDREN: ~ 2.5-12.5 H
DIBEKACIN NEONATE: ~ 10-45 H
NETILMICIN
TOBRAMICIN
STREPTOMYCIN 10-15 H PEAK 1-2 H AFTER IM PEAK 15-40
TROUGH < 5
ANTINEOPLASTICS
METHOTREXATE 12-24 H DEPEND ON DOSE & 24 H > 5 UMOL/L
DURATION OF INFUSION 48 H > 0.5 UMOL/L
72 H > 0.05 UMOL/L
IMMUNOSUPPRESSANTS
CYCLOSPORINE 1 D DAY 3 OR 4 OF THERAPY, THEN 100-200 UG/L
TWICE WEEKLY FOR FEW WEEKS
AND REDUCE TO EVERY 1-2 MO
Farmasi Klinis 22
DRUG TIME TO STEADY STATE SAMPLING TIME THERAPEUTIC RANGE
(MG/L)
ANTIARRHYTHMICS
DISOPYRAMIDE 1-2 D TROUGH 2-5
LIDOCAINE 1 H AFTER LD 2 H AFTER LD 1.5-5
5-10 H (NO LD) 6-12 H (NO LD)
PROCAINAMIDE/NAPA
ADULT (NO LD) IMMEDIATELY AFTER IV LD PROCAINAMIDE 4-10
: NORMAL RENAL 15-25 H 2 H AFTER START OF IV INFUSION, NAPA 6-20
: RENAL INSUFF 30-65 H ONCE MORE DURING 24 H PERIOD
ORAL: PEAK (1-4 H) AND TROUGH
QUINIDINE 2D TROUGH 2-5

CARDIAC GLYCOSIDES
DIGITOXIN 1 MO 8-24 H 13-25 UG/L
DIGOXIN 5-7 D 8-24 H 0.9-2.2 UG/L
MAY BE LONGER IN RENAL
INSUFFICIENCY Farmasi Klinis 23
DRUG TIME TO STEADY STATE SAMPLING TIME THERAPEUTIC RANGE
(MG/L)
ANTIEPILEPTICS
CARBAMAZEPINE 2-6 D TROUGH 4-10
ETHOSUXIMIDE 1-2 WK ANY TIME 40-100
PHENOBARBITAL 3 WK ANY TIME 15-40
PHENYTOIN 7D 2-4 H 10-20

VALPROATE 2-3 D TROUGH 50-100

BRONCHODILATORS
THEOPHYLLINE ADULT: 2 D IV: 30 MIN AFTER IV LD 10-20
CHILDREN: 1-2 D : 4-6 H AFTER BEGINNING THERAPY
INFANTS: 1-5 D : 12-18 H AFTER BEGINNING THERAPY
NEWBORN: 120 H ORAL: PEAK
PREMY: 150 H 2 H AFTER RAPID RELEASE PREP
4 H AFTER SUSTAINED RELEASE PREP
Farmasi Klinis 24
DRUG TIME TO STEADY STATE SAMPLING TIME THERAPEUTIC RANGE
(MG/L)
ANALGESICS
ASPIRIN 1-5 D 1-3 H 150-300 (ANTIINFLAM.)
250-400 (RHEUMATIC FEV)
PARACETAMOL 4 H POSTINGESTION > 200
TOXICITY 12 H POSTINGESTION > 50

PSYCHOACTIVE DRUGS
AMITRIPTYLINE 3-8 D TROUGH 150-250 UG/L
IMIPRAMINE 2-5 D TROUGH 150-250 UG/L
NORTRIPTYLINE 4-20 D TROUGH 50-150 UG/L
LITHIUM 3-7 D TROUGH 0.6-1.2 MEQ/L

Farmasi Klinis 25
 CONTOH SOAL

• Pasien PR, 54 tahun , TB 156 cm, BB 41 Kg. Masuk RS

didiagnosa pnemonia dan diterapi dengan gentamisin secara
IV 80 mg/12 jam. Pada hari kedua, darah pasien diambil untuk
diperiksa SCDnya dan diket : Cmak = 4,32 mcg/mL dan Cmin
= 0,9 mcg/mL.

• Pertanyaan : sesuaikah dosis yang diterima PR?

Farmasi Klinis 26
Penentuan keadaan steady state:

N = 6,5 (t1/2)
T

= 6,5 (2,5 jam)

12 jam

= 1,35

Farmasi Klinis 27
Db = 8 mcg/mL x 80 mg
4,32 mcg/mL

= 148, 15 mg ≈≈ 150 mg

Css = 150 mg/80 mg x 0,9 mcg/mL

= 1,7 mcg/mL

Farmasi Klinis 28
TERIMA KASIH

Farmasi Klinis 29