7. Faktor yang mempengaruhi
absorpsi
• Makanan:
-rifampicin
-phenoxymethyl penicillin
-erythromycin
• Obat lain:
-Antacid
-Anticholinergic
-Metoclopramide
• Penyakit saluran cerna/operasi
8.
9.
10. Digoxin : jumlah dalam tubuh 500 mcg
Konsentrasi dl. Plasma 0,78 mcg / L
500
Vd = = 641 L
0, 78
Quinacrine Vd 50.000 L
Frusemid Vd 7 L
Kloroquin Retina, hati
Tetrasiklin Tulang, hati
Digoxin Ginjal, hati, jantung
11.
12.
13.
14. Eradication of S.pneumoniae
• It is suggested that AUIC values for successful
pneumococcal eradication and prevention of
resistant development vary from 60 -250
• So the older quinolone such as ciprofloxacin or
levofloxacin are insufficient for eradication
• Moxifloxacin & gemifloxacin have sufficiently
high AUIC value (>150)
15.
16.
17.
18. Dosis ulang & konsentrasi steady state
• Bila interval pemberian obat > t ½
• Bila interval pemberian obat < t ½
• Bila interval pemberian obat = t ½
21. Biotransformasi fase I / Asintetik
–Oksidasi (cytochrome P450)
–Reduksi
–Hidrolisis
–Deamination
Biotransformasi fase II / Sintetik
konyugasi dengan :
Asam glucuronic
Asam asetat (Acetylation)
Glycin
Asam sulfat
Glutamin
22.
23.
24.
25. Induksi Enzym / Enzyme inducer
o Barbiturate :Barbiturate
Coumarin
Pil kontrasepsi
o Phenytoin : Dexamethasone
Pil kontrasepsi
o Merokok : Nicotine
(Nicotine ) Pil kontrasepsi
Theophyllin
o Rifampicin : Pil kontrasepsi
26. Enzyme Inhibitor / inhibisi enzim
o Chloramphenicol Phenytoin
Tolbutamide
o Cimetidine Chlordiazepoxide
Diazepam
Chlorazepate
Phenytoin
Theophyllin
30. Contoh menghitung loading dose
• Seorang pasien memerlukan Metronidazole
Mean Effective Concentration 6,25-8 mcg/ml (konsentrasi terapi)
Bioavailability (i.v=1, oral=95%, rectal=80%
Plasma half-life (t ½ )= 10 jam
Vd = 1L/kgBB
Berapa Loading dose i.v, atau rectal yang diberikan bila BB pasien
60 kg?
Berapa maintenance dose untuk setiap 8 jam, untuk pasien BB 60
kg, kalau diberikan peroral atau perectal?
31. Jawaban
• Loading dose = Vd x Cp / F
Vd = Volume of distribution
Cp = Konsentrasi terapi dalam plasma
F = Bioavailability
Loading dose i.v = 60 L x 6,25 mg/L /1
= 375 mg.
Loading dose oral = 60 L x 6,25 mg/L / 0,95
= 394 mg.
Loading dose rectal = 60 L x 6,25 mg/L / 0,60
= 625 mg.
32. Calculation of a maintenance dose:
-identikasi konsentrasi terapi
-penentuan dosis untuk maintenance
-penentuan interval dosis (setiap 8 jam, 6 jam dlsb)
• Maintenance dose = Vd x Cp x Di x 0,693 / t ½
-------------------------
F
Vd = Volume of distribution
Cp = Konsentrasi terapi
Di = Drug interval (interval dosis)
F = Bioavailability
33. • Maintenance dose oral tiap 8 jam untuk pasien 60 kg =
Vd x Cp x Di x 0,693 / t ½
----------------------
F
= 60L x 6,25/L x 8 x 0,693 / 10
-------------------------
0,95
= 218,8 mg
34. Disease and drug dosing
• Dosis obat perlu diubah bila:
. Obat > 80% dieliminasi oleh satu organ saja
(ginjal saja, atau hepar saja)
. Safety margin (IT) obat sempit
(lithium, digoxin, theophylline)
35.
36. Dosage in patient with renal impairment
• Standard loading dose
Patient’s CC
• Corrected dose = normal dose x --------------------
Normal CC (100 mL/min)
37. Corrected dose of drug with 2 route
of elimination (renal and liver)
• If a drug is cleared 50% by kidney, and 50% by liver. In
this patient the liver function is normal, but the function of
kidney is impaired with CC 20 mL/min. The normal
dosage is 200 mg/day.
• So the hepatic and renal clearance are each 100 mg/day
20 mL/min
• Corrected dose= 100 mg/day + 100 mg/day x-------------
100 mL/min
39. Drug dosing in the elderly
• Alter the Volume of distribution (Vd)
• Decline in cardiac output
• Decline in renal clearance
• Decline in hepatic extraction
• Decline in protein binding
• Disease in elderly
Reduction drug dose in elderly:
Digoxin Cimetidine Benzodiazepine
Gentamycin Tobramycin L-dopa
Phenytoin Valproate
Pethidine TCA