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    Farmakokinetik Sm. Iv

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    Chie Zhumie
    The document lists the staff and faculty of the Pharmacology Department at a university. It then provides definitions and key concepts in pharmacology including absorption, distribution, metabolism, excretion, pharmacokinetics, pharmacodynamics, and factors that influence drug dosing such as disease state, organ function, drug interactions, and patient demographics. Specific drug dosing calculations and adjustments for factors like renal impairment, liver disease, and elderly patients are also covered.

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    Farmakokinetik Sm. Iv

    Uploaded by

    Chie Zhumie
    40 views67 pages
    The document lists the staff and faculty of the Pharmacology Department at a university. It then provides definitions and key concepts in pharmacology including absorption, distribution, metabolism, excretion, pharmacokinetics, pharmacodynamics, and factors that influence drug dosing such as disease state, organ function, drug interactions, and patient demographics. Specific drug dosing calculations and adjustments for factors like renal impairment, liver disease, and elderly patients are also covered.

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    FARMAKOKINETIK SM. IV.ppt

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    The document lists the staff and faculty of the Pharmacology Department at a university. It then provides definitions and key concepts in pharmacology including absorption, distribution, metabolism, excretion, pharmacokinetics, pharmacodynamics, and factors that influence drug dosing such as disease state, organ function, drug interactions, and patient demographics. Specific drug dosing calculations and adjustments for factors like renal impairment, liver disease, and elderly patients are also covered.

    Copyright:

    © All Rights Reserved
    Download as PPT, PDF, TXT or read online from Scribd
    Download as ppt, pdf, or txt
    40 views67 pages

    Farmakokinetik Sm. Iv

    Uploaded by

    Chie Zhumie
    The document lists the staff and faculty of the Pharmacology Department at a university. It then provides definitions and key concepts in pharmacology including absorption, distribution, metabolism, excretion, pharmacokinetics, pharmacodynamics, and factors that influence drug dosing such as disease state, organ function, drug interactions, and patient demographics. Specific drug dosing calculations and adjustments for factors like renal impairment, liver disease, and elderly patients are also covered.

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    © All Rights Reserved
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    of 67

    Staf Farmakologi FK UNUD

    • Prof.Dr. I G.M. Aman, SpFK


    • Dr. Made Jawi, M.Kes
    • Dr. M.B. Toya Ariawan
    • Prof.DR. Dr. Tjok. Alit Kamar Adnyana, SpFK
    • Dr. W. Harsana, MS
    • Dr. I G.N. Anom Murdhana
    • Dr. I.B. Ngurah
    • Dr. Komang Satriyasa, M.Repro
    • Dr. Agung Wiwiek Indrayani, S.Ked
    • Ni Made Dwi Sandhi Utami, S.Si, Apt
    • Dr.Wayan Sumardika, S.Ked
    • Dr. I G.M.Surya Chandra Trapika, S.Ked
    PEGAWAI Laboratorium
    • Nyoman Sugiharta
    • Gde Wiranatha.
    FARMAKOLOGI
    • Farmakologi
    • Obat
    • Farmakokinetik
    • Farmakodinamik
    • Farmakoterapi
    • Posologi
    • Toksikologi
    • Farmakognosi
    • Farmasi
    Enabling outcome
    • Permeation process
    • Relative ease of permeation of weak acid or base form according to
    its pKa and the pH of the medium.
    • The common route of drug administration
    • Determinants of distribution of drug
    • Elimination of drugs (Zero & First Order Elimination)
    • Vd (Volume of Distribution)
    • Cl (Clearance)
    • Half life (t ½ )
    • First pass effect, Bioavailability, AUC (Area Under Curve)
    • MEC (Minimal Effective Concentration), MTC (Minimal Toxic
    Concentration), Peak and Trough Concentration, Steady State
    Concentration
    • Phase I & Phase II Biotransformation/ Metabolism
    • Enzyme Inducers, Enzyme Inhibitors
    Actions of a drug on the body.
    ( Pharmacodynamics )

    Body /
    Drug Living
    system

    Actions of the body on the drugs


    ( Pharmacokinetics )
    PHARMACOKINETIC

     ABSORPSI
     Distribusi
     Biotransformasi
    Ekskresi

    Asorpsi
    Distribusi

    Biotransformasi

    Ekskresi

    Terikat protein

    bebas
    Absorpsi
    • Difusi pasif (lipid difusion)
    • Filtrasi (aqueous difusion)
    − Transport aktif

    Difusi pasif Endocytosis

    Filtrasi

    C
    Transport
    aktif
    endocytosis
    Faktor yang mempengaruhi difusi :
    (lipid difusion)

    • Derajat keasaman
    • Derajat ionisasi
    • Kelarutan dalam lipid
    50 % terionisasi
    pKa obat 3,5 dl. pH 3,5
    50 % tak terionisasi

    9 % terionisasi
    dl. pH 2,5
    91 % tak terionisasi
     Obat gol. Asam Lemah

     Dalam suasana yang asam

     Lebih banyak dalam bentuk tak


    terionisasi (unionized)

     Mudah larut dalam lipid

     Mudah diabsorpsi (difusi pasif)


    Degree of ionization

    Weak base drugs

    Protonated unprotonated

    Ionized Unionizid

    Less lipid soluble More lipid soluble


    Percentage of ionized of drugs

    • For Weak Acid:


    % ionized= 100 /1+ antilog (pKa-pH)

    • For Weak Base:


    % ionized= 100 /1+ antilog (pH-pKa)
    Digoxin : jumlah dalam tubuh 500 mcg
    (dosis yang diberikan)
    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


    Biotransformation
    Obat yang larut dl. air

    Obat yang larut dalam lipid

    Hati
    Saluran cerna
    Paru

    ekskresi
    Ekskresi
    Biotransformation phase I / Asyntetic

    – Oxidation (cytochrome P450)


    – Reduction
    – Hydrolysis
    – Deamination
    Biotransformation phase II / Syntetic
    konyugasi dengan :
    glucuronate
    acetate (Acetylation)
    Glycine
    sulfate
    Glutathione
    Methyl groups
    Aspirin / Asetosal

    Salisilat

    Oksidasi glukuronik glisin

    Asam Salisilat salisilat salisilat


    gentisic glukorinik bebas urat

    Ekskresi
    Perubahan pada biotransformasi obat

    • Zat aktif Tidak aktif


    Acetaminofen Acetaminofen sulfate
    Aspirin Salysilate glucuronide

    Zat aktif Aktif


    Phenylbutazon Oxiphenbutazon
    Primidone Phenobarbital
    Codein Morphine
    Diazepam Desmethyl diazepam
    methyl oxazepam

    Zat tidak aktif Aktif


    Talampicillin Ampicillin
    Benorylate Paracetamol + acetosal
    First pass effect / eliminasi pra sistemik

    Sirkulasi sistemik

    Hati
    Obat

    Obat + metabolit

    Lignocaine propranolol
    Glyceril trinitrate morphine
    Determinants of biotransformation rate

    • Genetic factors
    < hydrolysis of ester (succinylcholine)
    < acetylation of amine (isoniazide)
    < oxidation (TCA)

    • Other drugs
    . Enzyme induction (phenobarbital)
    . Enzyme inhibition (cimetidine)
    . Intestinal P-glycoprotein inhibitors (verapamil)
    Enzyme induction / Enzyme inducer
    o Barbiturate : Barbiturate
    (phenobarbital) Coumarin
    Pil kontrasepsi
    o Phenytoin : Dexamethasone
    Pil kontrasepsi
    o Merokok : Nicotine
    (Nicotine ) Pil kontrasepsi
    Theophyllin
    o Rifampicin : Pil kontrasepsi
    o Carbamazepine: Warfarin
    Enzyme Inhibitor / inhibisi enzim
    o Chloramphenicol Phenytoin
    Tolbutamide

    o Cimetidine Chlordiazepoxide
    Diazepam
    Chlorazepate
    Phenytoin
    Theophyllin
    o Ketokonazole
    o Grapefruit juice
    o Ritonavir
    Dosis ulang & konsentrasi steady state
    • Bila interval pemberian obat > t ½
    • Bila interval pemberian obat < t ½
    • Bila interval pemberian obat = t ½
    Ekskresi obat

    • Ginjal
    • Saluran cerna
    • Paru-paru
    • Keringat
    • Air mata
    • Air susu
    Ekskresi lewat ginjal

    • Filtrasi glomerulus

    • Sekresi tubulus

    • Reabsorpsi
    • pH. Urine yang asam mempercepat ekskresi obat
    gol. Basa lemah.
    • pH. Urine yang asam memperlambat ekskresi obat
    gol. Asam lemah.

    • Phenobarbital (gol.asam lemah). Kalau ingin mempercepat ekskresinya


    lewat urine, apakah tindakan kita?

    apakah diberikan amonium kloride (asam) ataukah diberikan natrium


    bikarbonas (basa) ?. Coba jelaskan !
    Faktor yang mempengaruhi absorpsi

    • Makanan:
    -rifampicin
    -phenoxymethyl penicillin
    -erythromycin
    • Obat lain:
    -Antacid
    -Anticholinergic
    -Metoclopramide
    • Penyakit saluran cerna/operasi
    Aplikasi farmakokinetik dalam klinik

    • Menentukan loading dose


    -Antibiotic
    -Anticoagulant
    -Antiepileptic
    -Antiarrhythmic
    -Antiasthmatic
    -Antihypertensive
    • Menentukan maintenance dose
    • Merencanakan interval dose
    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?
    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.
    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
    • 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
    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)
    Dosage in patient with renal impairment

    • Standard loading dose


    Patient’s CC
    • Corrected dose = normal dose x --------------------
    Normal CC (100 mL/min)
    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
    Dosage in liver disease

    Tergantung BSP retention


    • BSP retention < 5% (No Liver Damage)
    • BSP retention 5-25% (Mild Liver Damage)
    dosis maintenance dikurangi 25-50%
    • BSP retention 25-75% (Severe Liver Damage)
    dosis mainenance dikurangi 50-80%
    • BSP retention >75% (Very Severe Liver Damage)
    dosis maintenance dikurangi 80%
    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
    Faktor yang mempengaruhi Filtrasi
     berat molekul obat, <100

    Faktor yang mempengaruhi transport aktif


     ada karier yang sesuai
    .Levo Dopa
    .Fluorouracil
    .Penicilin
    .Probenecid
    jaringan otak

    Glial cell

    Tidak ada pori

    Blood Brain Barrier


    ( sawar darah otak )
    Pengaruh perubahan pH
    • Basa lemah pKa 7,5 – 10
    • Asam lemah pKa 3,0 – 7,5

    Amphetamin Basic Quinidin


    drug PH 6 – 7
    Salicylate acid
    Phenobarbital drug
    Kompetitip pada proses sekresi renal

    • Benzyl Penicillin
     probenecid
     Phenylbutazone
     Sulphinpyrazone
     Aspirin
     Indometacine
    . Nitrofurantoyn
    Ekskresi lewat paru-paru

    • Obat yang mudah menguap ( cair, gas )


     Anestetik umum
     Alkohol
     Amonium kloride
    Waktu paruh obat ( t1/2 )

    • t 1/2 dipengaruhi oleh :


     difusi obat ke jaringan
     ikatan dengan plasma protein
     Ikatan dengan jaringan
     biotransformasi Hati
     Ekskresi ginjal
    Bioavailabilitas
    ( AUC ) oral
    Bioavailabilitas
    ( AUC ) I.V

    Faktor yang mempengaruhi


     Faktor biologis
     Faktor farmasi
    • Farmasi
     partikel obat
     cara pembuatan
     bahan pelarut
     kombinasi obat
    Ekskresi melalui ASI

    • Anti thyroid
    • Anti psychosis
    • Anti kanker
    • Anti biotika
     Chloramphenicol
     sulphonamide
     Kanamycin
     Streptomycin
     Tetracycline
    Konsentrasi steady state / plateau

    • Jumlah obat masuk = jumlah eliminasi


    • Dicapai dalam 4 X pemberian dengan
    interval waktu sama dengan waktu paruh
    obat
    Pemberian obat dengan t ½ panjang
    Digoxin t ½ = 48 jam ( 2 hari )
    Cara pemberian obat
    Peroral (enteral)
    Faktor yang mempengaruhi :
    * Ionisasi obat
    * lipid soluble
    * derajat keasaman ( ph )
    * berat molekul
    * pengosongan lambung

    Kebaikan :
    # mudah diberikan
    # tidak perlu steril
    # kontak langsung dng. Infeksi saluran cerna
    Kejelekan :

    # dirusak dilambung
    # absorbsi sulit diduga
    # obat basa kuat
    # iritasi saluran cerna
    Cara pemberian parenteral

    • Intracutan
    • Subcutan
    • Intra muscular:
    -phenytoin
    -diazepam
    • Intra vena:
    -jantung
    -ginjal
    • Intra arteriil:
    -nitrogen mustard
    • Intrathecal
    Cara pemberian lewat mucosa
    * Sublingual
    * Perectal
    * Mucosa lokal

    Cara pemberian inhalasi


    * Gas / cairan yg mudah menguap
    * Aerosol
    * Serbuk halus

    Cara pemberian lewat kulit

    Cara pemberian Transdermal

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