FARMAKOTERAPI I

Epilepsi
Presented By :
Ekanita Desiani

Program Studi S1 Farmasi Universitas Pekalongan

 Definition
n Epilepsi (WHO) :

kelainan otak kronik dgn berbagai causa

serangan epilepsi (seizure) berulang
ok bangkitan neuron berlebihan
 Gb klinis
 kejang
 perubahan tingkah laku
 perubahan kesadaran
 Definition
 Seizure :
– Manifestasi klinik dari bangkitan
hipersinkron, berlebihan dan abnormal
yang bersifat mendadak (paroxysmal)
dari populasi neuron kortek
 Epilepsi :
– Suatu kelainan neurologik yg bersifat
kronik dan ditandai seizure berulang
(recurrent seizure)
 Definition

 Status Epilepticus :
 Keadaan dimana serangan epilepsi
berlangsung lama ( > 30 menit )
 serangan epilepsi (seizure)
 berkali kali, serangan berlangsung
rata-rata + 2 menit
 kesadaran diantaranya tak pulih
 Etiology
Primary - Idiopathic

Symptomatic or Cerebrovascular

Cryptogenic (23%)
CNS Neoplasma
5% 4% 4%
4%
3%
2% Congenital CNS
1%
Malformation
Trauma

CNS Infection

77% Other known

Primary – Idiopathic Birth asphyxia

(77%)
 Causes of Seizures as a
Function of a Age at Onset

Simon, et al., Clinical

Neurology 7th ed
 Mekanisme Dasar Epilepsi
l 1. Altered neurotransmitter balance
• Increased glutamate ( excitatory )
• Decreased GABA ( inhibitory )
• Altered neuromodulator activity
l 2. Altered ionic homeostasis – K, Ca, Chloride
l 3. Rearranged neuronal circuits
• loss of inhibitory synapses
• Overgrowrth of excitatory synapses
• Simplified circuits that improved neuronal
synchronization
 Klasifikasi epilepsi
ILAE 1989
 Partial epilepsy
– Idiopathic • simple partial
– Symptomatic • complex partial
• secondary generalized
– Uncertain etiology
 Generalized epilepsy
– Idiopathic
– Symptomatic - West sy, Lennox gastaut
 Epilepsies undertemined focal or generalized
 Special syndromes
– Febrile convulsion
– Acute metabolic dearengement
8
International
Classification of
Epileptic Seizures

Dipiro, et al. 2008.

Pharmacotherapy A
Pathophysiology Approach
7th Ed.
 Partial (focal) Seizures
I. Simple Partial Seizures
 Focal motor, gangguan sensory /speech
 Terbatas pada single limb /grup otot. Seizure-
symptoms tdk berubah selama seizure.
 Tak kehilangan kesadaran

II. Complex Partial Seizures

(Temporal Lobe epilepsy or Psychomotor
Seizures)
• Confusion, gangguan perilaku.
• Motor activity merupakan non-reflex actions.
• Manifestasi klinik bervariasi.
• Kehilangan kesadaran.

EEG: Bizarre generalized EEG activity with

evidence of anterior temporal lobe focal
abnormalities.
 General Seizures
I. Absence Seizures (Petite Mal)
 Kehilangan kesadaran singkat dan tiba tiba .
 Umumnya symmetrical clonic motor activity
(occasional eyelid flutter to jerking of the
entire body).
 Biasanya tidak ada manifestasi motorik.
 Serangan sangat singkat (5-10 detik), tetapi
dapat berkali kali dalam sehari .
 Seringkali dimulai masak kanak kanak
(daydreaming attitude, no participation, lack
of concentration).

EEG: Bilaterally synchronous, high voltage, 3-per-second

alternating spike and wave pattern.
II. Generalized Tonic-Clonic Seizures

Major convulsions, biasanya dengan 2

fase:
Fase Tonic:
- sustained powerful muscle contraction (meliputi
seluruh otot tubuh ) yang menghentikan pernafasan .
Fase Clonic :
- ada fase alternatif antara contraction dan
relaxation,
dapat berupa pergerakan bilaterally symmetrical
atau “running” movements.
EEG: Recruitment of neurons throughout the cerebrum.
Tonic (HF, HV, SA), clonic (SF, HV), and post-ictal
phases.
III. Atonic Seizures (atypical)
 Kehilangan postur tonus tubuh,
dgn kehilangan kekuatan menyanggah
kepala (head falling).

IV. Tonic Seizures

 Opisthotonus, kehilangan kesadaran,
dan perubahan manifestasi autonomic
V. Clonic Seizures
Kontraksi klonik yang rhythmic dari seluruh otot
tubuh, kehilangan kesadaran, adanya tanda tanda
perubahan manifestasi otonomik .

VI. Myoclonic Seizures

Isolated clonic jerks yang berkaitan dengan
loncatan yang singkat (brief bursts) dari multiple
spikes pada gambaran EEG.

VI. Infantile Spasms

Suatu epileptic syndrome, serangan dalam bentuk
fragmentary atau kadang kadang bilateral.
Ditandai oleh adanya brief recurrent myoclonic
jerks dari seluruh bagian tubuh dengan adanya
flexi atau extensi yang tiba tiba dari tubuh atau
ekstrimitas .
Quality Standards
Subcommittee of the American
Academy of Neurology. Practice
parameter: A guideline for
discontinuing antiepileptic drugs
in seizure free patients [summary
The best
statement]. Neurology quality of
1996;47:600–602.
 Brodie MJ, French JA.
life is complete
Management of epilepsy in associated elimination
adolescents and adults. Lancet with a of seizures
2000;356:323–328.
 Garnett WR. Antiepileptic drug seizure-free
treatment: Outcomes and state.
adherence. Pharmacotherapy
2000;20:191S–199S.

no side effects
with an optimal
quality of life.
Oral Anti Epilepsi
 Generalized seizure

• Tonic clonic seizure

– Lini I : CBZ, OxCBZ, Valproate
– Lini II : Bensodiazepin drugs
– ADD : DPH, Lum, primidone
• Absence seizure
– Lini I : Valproate
– Lini II : Ethosuximide,Bensodiazepin
– ADD : Acetazolamide
p Partial seizure

– Lini I : CBZ. OxCBZ, Valproate

– Lini II : Bensodiazepn, Vigabatrin

– Add : DPH, Lum, primidone

 Status Epileptikus

harus segera distop ok

n Semakin lama seizure

– semakin sulit dikontrol &
kerusakan otak >
n Kerusakan sel otak ok bangkitan
eksitasi yg terus menerus
n Faktor sistemik --- kerusakan sel otak
n Ok itu status harus distop dlm 30
menit
 Algoritma
Status Epileptikus
0 - 10 menit
l Amankan jalan nafas
l Monitor tanda vital
l Ambil darah utk ph, O2, CO2,
glukosa, elektrolit, kadar OAE
l Infus 0.5 saline
l Beri vit B1 dan B6 25-50 cc dlm
50 % glukosa
 10 - 20 menit (4 pilihan)

l Pilihan A :
– IV DPH 15-20 mg / kg --- 50 mg /menit
dlm 0.5 saline.
l Pilihan B :
– Diasepam 0.1-0.2 mg / kg --2-3 mg/menit IV
– + IV DPH 15-20 mg /kg,-- 50 mg / menit dlm 0.5
saline -
– ulangi diasepam ssdh 20 menit KP
l Pilihan C : Lorasepam IV 0.15 mg/kg, 2-3 ‘
l Pilihan D :
– Luminal 15-20 mg/kg -- 100 mg/menit dlm
0.5 saline
 > 30 menit

l Pindahkan ke ICU
l Intubasi dan ventilasi
l Monitor EEG, EKG, tekanan darah
l Burst supression EEG pattern
– Thiopental bolus 20-30 mg/kg diikuti
drip 0.5 mg/kg permenit
– Phenobarbital bolus 0.05 mg/kg diikuti
drip 0.1 mg/kg
27
CASE STUDY
Patient Profile
Nama : Tn. ES

No. DMK : 12.18. xxxx

Alamat : Kyai Hasan

Status : Askes wajib

Usia/BB/TB : 60 th/ 80 Kg/ 165 cm

MRS/KRS : 18-10-12/ 31-10-12

Ruang : Seruni B
Patient Profile
Diagnosa KRS
Alasan MRS RPD
Epilepsi
Diagnosa
Dx utama : Post stroke
Kejang mendadak 3 • Stroke I : 10 th yll infark
• Dx klinis: cephalgia,
jam SMRS, durasi vomitting, lateralisasi
Komplikasi:
kejang 30’ dg mata • Stroke II : 9 bln yll
(D),S.epileptikus
status local
terbelalak ke atas. • Stroke III : 8 bln yll
Dxsecondary
Sekunder: generalize
HT + AKI
Diawali muka merot • HT : 10th yll tdk tonic clonic seizure
kemudiian tangan & terkontrol • Dx tropis : Subcortex-
kaki menghentak. • Riwayat Obat cortex (S)
Lidah menggigit (+), Terapi
• Dx KRS
etio : chronic
mulut berbusa (+), • Amlodipin 1x5mg cerebral infarction
Fenitoin 3x100 mgpd
ngompol (+), BAB • Sohobion 1x1 capsula externa
Amlodipin (S)
5mg-0-0
BAK normal. • Betahistin 3x6 Post stroke epilepsi
ASA 0-1 tab-0
No Data Klinik Tanggal (Oktober 2012)
18 19
20 21 22 23 24 25 26 27
(IRD) (S-B)
1 Suhu tubuh (T) 36,7 37 36,5 36,5 36,6 36 36,5 37 37 37
2 Tekanan darah 140/ 150/ 140/ 170/
140/80 160/80 140/80 140/80 150/90 150/90
(TD) 100 100 100 100
3 Nadi (N) 84 92 84 84 92 84 87 86 87 87
4 Sesak + + - - - - - - - -
5 GCS 315 315 456 456 456 456 456 456 456 456
6 Kejang + + - - - - - - - -
7 Defekasi + + + + + +
8 PU 600 2300 1300 1700

No Data Klinik Tanggal (Oktober 2012)

28 29 30 31
1 Suhu tubuh (T) 37 36 36 37
2 Tekanan darah 140/ 160/ 140/
140/80
(TD) 90 120 80
3 Nadi (N) 84 84 85 92
4 Sesak - - - -
5 GCS 456 456 456 456
6 Kejang - - - -
7 Defekasi + + + +
8 PU 600 2300 1300
 Tanggal (Oktober 2012)
Data Nilai Normal
18 19 20 23 25 28 30
GDA < 200 mg/dl 137 112
GDP <100 mg/dl 77
BUN 5-23 mg/dl 11,7 13 13 12 12
Creatinin <1,2 mg/dl 1,4 1,6 1,7 1,7 1,6
AST 0 – 2x 38 u/L 19
ALT 0 – 2x 41 u/L 25
Albumin 3,8-4,4 g/dl 4,79
Na 135 –145 mmol/L 146 139
K 3,8 – 5,0 mmol/L 3,6 3,4
Cl 97-103 mmol/L 101 105
Ca 8,5-10,1 mmol/L 18,8
RBC 4,00 – 6,00.106/μL 4,79 5,48
Hb 11,0 – 18,0 g/dL 14,5 16,0
WBC 4,5–10,5x 10³ /mm³ 11,9 11,7
HCT 35-60% 41,4 46,9
MCV 80,0-99,9 mm3 86,8 85,6
MCH 27-31 pg 30,4 29,1
MCHC 33-37 g/dl 35,0 34,0
150-450 x
PLT 103/mm3
133 238

Bil. direct < 0,20 g/dl 0,23

Bil.tot 0,3-1,0 mg/dl 1,12
Tot. Prot 6,3
Tot. Kol 00-200 154
TG 30-150 66
HDL 40-60 47
LDL 00-99 93
Data Konsul

Konsul Cardio Konsul IPD

Px dg stroke 3th attack + Px dg stroke infark trombotik

GTCS + HT + HT + pe↑ an serum
kreatinin (1,7) mohon
Jawaban: evaluasi
Didapatkan px dg HT st. I
JNC VII tanpa tanda-tanda Jawaban
gagal jantung akut
Saran:
Saran: Lakukan pemeriksaan ulang
Tx amlodipin 5mg-0-0 SK → Hasil dikonsul ulang ke
diteruskan IPD
Data BGA

Tanggal
Nilai Normal (Oktober 2012)
18
Ph 7,35-7,45 7,16
PCO2 25-45 70
PO2 35-45 248
BE ecf (-)3,5 – (+) 2 -3,7
HCO3 22-26 25,0
TCO2 15-22 vol % 27,1
SO2 95-100% 100
Pemeriksaan Urine
Lengkap
Data Urine Nilai Tanggal (Oktober 2012)
Normal 24 30
SG 1,010-1,015 1,004 1,006
PH 5-8 6 5
Leu - - -
Nit - - -
Prot - - -
Glu Norm Norm Norm
Ket - - -
UBG Norm Norm Norm
Bil - - -
Ery - 10 -
Colour - Yellow Yellow
Clarity - Clear Clear
Ery (Mikr.) 0-2 1-2 -
Leu (Mikr.) 0-5 Banyak 0-1
Epitel (Mikr.) Sedikit 2-3 0-1
Kristal (Mikr.) - - -
Lain-lain - - -
Pemeriksaan Lain

Foto Thorax AP

Cor : besar & bentuk kesan normal

Pulmo: tdk tampak infiltrat
Sinus phrenicocostalis kanan & kiri tajam
Kesan : saat ini cor & pulmo tdk tampak kelainan

CT Scan Axial tanpa kontras

Kesimpulan :
Chronic ischemic cerebral infarction pada kapsula
externa kiri
PROFIL TERAPI
 Jenis Obat Tanggal (Oktober 2012)
N Nama Regimen
18
o Dagang/ Dosis 19 20 21 22 23 24 25 26 27 28 29 30
(IRD)
Generik
1 O2 masker 6 lpm v
2 Inf. NS 0,9% 1500 cc/hr v v v v //
Inj. Prn kejang v
3 v v v v v
Diazepam 1 amp (rect)
Loading
(15-18
v
mg/Kg BB)
4 Fenitoin
i.v → 1200mg
Maintenance v
v v v v v v v v v v v
(3x100 mg) (p.o)
Inj.
5 3x1 amp v v v //
Metamizole
5mg-0-0
6 Amlodipin v v v v v v v v v v v v v
(p.o)
1x100 mg
7 ASA v v v v v v v v
(p.o)
8 Inj. Ranitidin 2x1 amp v v v v v v v v v //
Inj.
9 3 gr v v //
Piracetam
Inj. CDP
10 3x250 mg v v v v v v v v v v
Cholin
11 Inf. PZ v v
DISCUSSION
Antiepileptic Drugs
 Neuronal
Sites of Action
of
Antiepileptics

Luellmann, 2005.
Color Atlas of
Pharmacology
Start drugs dose administration stop indication monitoring

19/11 Phenytoin 3x100mg Injection to a large - plasma level,

vein,max rate is 20- blood, liver
50mg/min, an in line 0,22- function, sign
5 micron filter is of toxicity
recommended for IVPB (confusion,
solution due to high loss of motor
potential for precipitation coordination,
of solution. Avoid nystagmus)
extravasation, following Seizure
i.v administration PZ management
should be injected trough
the same needle or i.v
catheter to prevent
irriitation
18/10 diazepam 1amp Max rate 5mg/min by 23/11 Respiratory,
(Prn direct i.v injection into cardiovascular
seizure) large vein, avoid , mental status
extravasation

No Data Klinik Tanggal (Oktober 2012)

18 19
20 21 22 23 24 25 26 27-31
(IRD) (S-B)
1 GCS 315 315 456 456 456 456 456 456 456 456
2 Kejang + + - - - - - - - -
 Summary of Anticonvulsant
Drug Therapy
Drug Usual Loading or initial Maintenance Therapeutics
Preparation Dose Dose Serum Levels
Phenytoin 100-mg Oral loading: 1000 mg 300-400 10-20 µg/ml
capsule. in two to four divided mg/day in a
Also 30-mg doses over 12-24 hours single dose or
capsule, 50-mg divided doses
Intravenous loading:
tablet 1000-1500 mg (15-18
mg/kg) not exceeding 50
mg/min Fosphenytoin is
prodrug form for
intramuscular or
intravenous use

Simon, et al., Clinical Neurology 7th ed

Dipiro, et al. 2008. Pharmacotherapy A
Pathophysiology Approach 7th Ed.
Disease States and Conditions that Alter
Phenytoin Plasma Protein Binding

McGrawHill, 2008. CLINICAL USEFULNESS OF UNBOUND

PHENYTOIN CONCENTRATIONS
Diagnosis & Management of Epilepsy in Adults
(A National Clinical Guidelines 2003)

Generalised Tonic Clonic

Status Epilepticus
Antihypertensive
Drugs
JNC 7, 2003
Saseen, JJ & Maclaughlin, EJ 2008, 'Hypertension' in Pharmacotherapy a pathophysiologic
approach , 7th Ed., eds D Joseph, T Robert, Y Gary, M Gary, W Barbara & P Michael, The
McGraw-Hill Companies, Inc., New York
Algoritma Terapi
Hipertensi Akut
pada Pasien
dengan Stroke
Clinical Trial and Guideline Basis For Compelling
Indications For Individual Drug Classes

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and
Treatment of High Blood Pressure 2004
Calcium Channel Blocker’s Mechanism of Action
 Drugs T1/2 OOA Excretion Disposition
(hrs) (route)
Dyhidropyridines
Amlodipin 30-50 30-50 mnts Urine (10% > 90% bound to plasma
as parent; proteins; extensively
60% as metabolized
metabolite)
Nifedipin 4 < 1 minute (IV), 80% of the About 90% bound to
5–20 minutes drug plasma
(sublingual or and protein; metabolized to an
oral) metabolites acid lactate.
excreted in
urine.
Nicardipine 2-4 20 mnts (oral) Urine, feces 95% bound; extensively
metabolized in the liver.
Nimodipine 1-2 0.5-2 hrs (oral); Urine (50%); Extensively metabolized.
10 mnts (IV) feces (32%)

Katzung, 2007; Lacy, et al., 2010

 Tgl Terapi Do Do literatur Keterangan Monitoring
Regimen
18/10/ Amlodipin 5mg-0-0 2.5-10 mg Amlodipin digunakan Tekanan
12 - (p.o) once daily sebagai terapi antihipertensi darah
KRS pada pasien dengan stroke
dimana bekerja dengan
menghambat influks Ca.
Namun berdasarkan JNC-7,
terapi antihipertensi pada
pasien dengan stroke &
kidney disease lebih
direkomendasikan
penggunaan ACEI

Data Klinik Tanggal (Oktober 2012)

18 19
20 21 22 23 24 25 26 27
(IRD) (S-B)
Tekanan darah 140/ 150/ 140/ 170/
140/80 160/80 140/80 140/80 150/90 150/90
(TD) 100 100 100 100
Data Klinik Tanggal (Oktober 2012)
28 29 30 31
Tekanan darah 140/ 160/ 140/
140/80
(TD) 90 120 80
Antiplatelet
 Regimen Tgl
Obat Dosis Literatur Tgl Mulai Monitoring
Dosis Stop
ASA 1X100 mg Stroke/TIA 23/10/12 - PLT , nyeri
(noncardioembolic;
(p.o) secondary prevention):
epigastrik
Oral: 50-325 mg once daily
(Adams, 2008) or 50-100 mg
once daily

Acute ischemic stroke:

Oral: 150-325 mg once daily

Data Lab Normal 18 20

PLT 150-450 x 133 238
103/mm3
Sacco et al. 2006, 'Guidelines for prevention of stroke in patients
with ischemic stroke or transient ischemic attack', Stroke, vol. 37,
pp. 577-617;
Adams et al. 2007, 'Guidelines for the early management of adults
with ischemic stroke', Stroke, vol. 38, pp. 1655-1711
Sacco et al. 2011. Guidelines for the Prevention of Stroke in Patients With
Stroke or Transient Ischemic Attack. Stroke, Vol. 42, p. 227-276.
 Treatment For
Neuroprotectant
THE ROLE OF VARIOUS NEUROPROTECTIVE AGENTS
ON THE ISCHEMIC CASCADE

Fisher, M & Schaebitz, W 2000, 'An overview of acute stroke therapy', Archives of Internal
Medicine, vol. 160, pp. 3196-3206
Tanggal Terapi Mekanisme Kerja Monitoring
20- CDP • Citicoline adalah molekul organik yg berfungsi sbg Fungsi
intermediet dlm biosintesis fosfolipid membran sel Kognitif
29/10/12 Cholin • Citicoline dikenal sbg nukleotida yg berperan penting dlm
metabolisme seluler
• Citicoline mampu memperbaiki membran neuronal
melalui pe↑ sintesis fosfatidilkolin
• Citicoline mampu memperbaiki kerusakan neuron
kolinergik melalui potensiasi produksi asetilkolin
• Citicoline mampu menurunkan asam lemak bebas pada
area stroke yg diinduksi oleh kerusakan saraf

Richard Conant, MAc, CN, and Alexander G. Schauss Therapeutic

Applications of Citicoline for Stroke and Cognitive Dysfunction in
the Elderly: A Review of the Literature Altern Med Rev
2004;9(1):17-31
 Obat Level Signifikan Keterangan
Phenytoin + Significant → Phenytoin will decrease the level or effect of
Diazepam Monitor Closely diazepam by affecting hepatic/intestinal
enzyme CYP3A4 metabolis. Significant
interaction possible, monitor closely
Phenytoin + Minor Phenytoin will decrease the level or effect of
Amlodipine amlodipin by affecting hepatic/intestinal
enzyme CYP3A4 metabolism. Minor or non-
significant interaction
Ranitidine + Minor Ranitidine increase levels of phenytoin by
Phenytoin decreasing metabolism. Minor or non-
significant interaction
 Pemilihan terapi antiepilepsi pada pasien sudah sesuai dengan
guideline. Hanya saja perlu dipertimbangkan untuk pemilihan
Lorazepam karena berdasarkan penelitian & guideline yang
sudah ada penggunaan Lorazepam pada pasien dengan status
epilepticus dianggap lebih efektif dibandingkan penggunaan
diazepam/fenitoin tungal maupun kombinasi

 Pasien mendapatkan terapi anti kejang feniton dimana

penggunaannya jangka panjang yang dapat menginduksi
terjadinya defisiensi folat, maka sebaiknya pasien diberi terapi
tambahan asam folat

 Pemilihan terapi antihipertensi amlodipin berdasarkan JNC-7

dimana dengan compailling indication stroke & kidney injuri lebih
disarankan penggunaan golongan ACEI
 PROPOSED MAJOR PATHWAY OF
CITICOLINE NEUROPROTECTION

ArAc, arachidonic acid; GSH,

glutathione; nSMase, neutral
sphingomyelinase;
PLA2 phospholipase A2;
PtdCho, phosphatidylcholine;
ROS,
reactive oxygen species

Adibhatla, RM, Hatcher, JF & Dempsey, RJ 2002, 'Citicoline: neuroprotective mechanisms in cerebral ischemia', Journal of
Neurochemistry, vol. 80, pp. 12-23
 Biosynthesis of Acetylcholine, Phosphatidylcholine (PtdCho),
S-adenosyl-L-methionine (AdoMet), and Glutathione (GSH)

Adibhatla, RM, Hatcher, JF & Dempsey, RJ 2002, 'Citicoline:

neuroprotective mechanisms in cerebral ischemia', Journal of
Neurochemistry, vol. 80, pp. 12-23
Recent Studies (since 1995) Investigating the Action of Citicoline
in Neuropathological Conditions

Adibhatla, RM, Hatcher, JF & Dempsey, RJ 2002, 'Citicoline: neuroprotective mechanisms

in cerebral ischemia', Journal of Neurochemistry, vol. 80, pp. 12-23
 Mechanism Action Of Citicholin

Adibhatla, RM, Hatcher, JF & Dempsey, RJ 2002, 'Citicoline: neuroprotective mechanisms in cerebral ischemia',
Journal of Neurochemistry, vol. 80, pp. 12-23
Luellmann, 2005. Color Atlas of Pharmacology
Simplified Synopsis of Drug Interaction Properties of
Common AEDs
Luellmann, 2005. Color Atlas of Pharmacology
Steady State Concentration
Desired Cp~ fraction (%) Cp~ Fraction Constant

90 3,32
95 4,32
99 6,65

e.g to achieve 90% steady state concentration of phenytoin

we need
Css = 3,32 x t ½
= 3,32 x 22h
= 73,04h or 3 days
• Css is the steady state concentration of pheytoin
• T ½ is the average half life of phenytoin
Phenytoin Maintenance Dose Calculation

Bauer, LA 2008, Applied Clinical Pharmacokinetics 2nd ed, McGrawHill New York
 Phenytoin
 Vmax is the maximum rate of Maintenance Dose
metabolism in mg/d
 S is the fraction of the phenytoin
Calculation
salt form that is active phenytoin
(0.92 for phenytoin sodium • Km is the substrate
injection and capsules; 0.92 for concentration in mg/L (which
fosphenytoin because doses equals μg/mL) where the rate
are prescribed as a phenytoin of metabolism = Vmax/2
sodium equivalent or PE, 1.0 for Michaelis Manten parameter:
phenytoin acid suspensions and • Adult with normal kidney and
tablets) liver function
 MD is the maintenance dose of Vm = 7 mg/kg/day
the phenytoin salt contained in Km = 4 µg/ml
the dosage form in mg/d
• 6 m.o-6 y.o
Vm = 12 mg/kg/day
 Css is the phenytoin Km = 6 µg/ml
concentration in mg/L (which • 7-16 y.o
equals μg/mL) Vm = 9 mg/kg/day
Km = 6 µg/ml
 Klirens Kreatinin
18 23 25 28 30
Kreatinin 1,4 1,6 1,7 1,7 1,6

CrCl : (140-umur) x BB
72 x kreatinin

CrCl 63,5 55,56 52,29 52,29 55,56