8 Epilepsy & TDM

1. Drug related problem (DRP)

failure to receive prescribe drug : Non compliance
Side effect Phenytoin

2. SOAP Note
Problem list : Generalize tonic clonic seizure
Subjective data
CC: 28


HPI :

3
4
diazepam 10 mg

PMH : epilepsy x 5
SH : denies alcohol and tobacco use

Objective data
MH : phenytoin 400 mg po qd
PE : VS: BP 160/98, HR 110, RR 20, T37.5, Wt 55 kg, Ht 160 cm

HEENT : bite wound on tongue, moderate gingival hyperplasia CHEST:

clear
COR : normal S1, S2, no S3, S4
EXT : moderate joint swelling of hands and feet
NEURO : unresponsive to deep pain
LABS :
phenytoin 4.0
Assessment :



(postictal phase) Generalized tonic clonic seizure
drug of choice carbamazepine, phenytoin,
phenobarbital, valproate
phenytoin 400 mg QD

phenytoin

50-100 g/ml 40
g/ml

drug of choice
carbamazepine, phenobarbital, valproate

Plan :
Therapeutic plan : carbamazepine 400 mg divide in 2 dose
Therapeutic goal : ,

Efficacy monitoring :
-
carbamazepine level 4-12 g/ml
ADR monitoring :
- Carbamazepine : diplopia, nausea, headache, dizziness, peripheral
neuropathy
Future plan :
- / 5-10

Patient education :
-

-
-

3.

Carbamazepine
category D
folic acid 5 mg neural tube
defect
folic acid 5 mg 12
weeks
36 weeks oral vitamin K 20 mg/day

vitamin K 1 mg IM

2

1.
status
epilepticus

 54
1
2 30 ER


status epilepticus
2. status epilepticus



1-2 General examination spider
nevi



6-72
7-8
50 g/day
status epilepticus Alcohol withdrawal
3.
(long-term AEDs)

- check airway blood circulation oxygen oxygen
mask EEG
- IV fluid BS, CBC, Electrolyte
LFT IV fluid 50% glucose 50 ml vitamin B1 (pabrinex)
100 mg IV stat
- Diazepam (Valium) 10 mg IV push Lorazepam 0.1
mg/kg IV push (rate 2 mg/min) diazepam dose 15

1
- loading dose Antiepileptic
phenytoin
20 mg/kg slow iV push ( rate 50 mg/min)

- 30 loading dose
phenytoin 10 mg/kg (maximum dose = 30 mg/kg)
- 60
refractory status epilepticus ICU EEG, oxygen saturation
EKG
-
2nd antiepileptic drugs Midazolam (IV bolus), Propofal (IV
bolus & infusion), pentobarbital (IV bolus & infusion), thiopental (IV bolus &
infusion) topiramate (ng) continuous infusion 1st
antiepileptic drugs
- 24 2nd
antiepileptic drugs 50% 24

1 phenytoin, phenobarbital
valproate phenytoin 100 mg/day 6-8 . PO

- Vitamin B complex
13 po pc
13 po pc
- Phenytoin 100 mg po q 6-8 hr

- Diazepam 5 mg

3 TDM of Phenytoin
30 68 . 170 .
10
Phenytoin
(Dilantin100 mg/cap) 2 2
Phenytoin (Dilantin100 mg/cap) 3

Phenytoin ( phenytoin level 8 mg/L)
1

mild ataxia mild nystagmus Phenytoin
20 mg/L

 2 :
Lab test
Date 26/6/52 Date 28/8/52
BUN (7-17 mg/dL)
16
17
Scr (0.6-1.2 mg/dL)
0.8
0.9
Serum albumin (4.2-5.4 mg/dL)
4.4
4.8
Phenytoin 2 :
Date Dosage regimen
Measured drug level
9/12/57 200 mg hs
8 mg/L
9/2/58
300 mg hs
20 mg/L
Plasma therapeutic concentration of Phenytoin: 10-20 mg/L

1. phenytoin
serum albumin normal range serum
phenytion
9/12/57

Dilantin100 mg/cap 2 phenytoin (Css)
8 mg/L Subtherapeutic range 9/2/58
Dilantin100 mg/cap 3 Css
phenytoin 20 mg/L Borderline of toxic level

mild ataxia mild nystagmus
2. pharmacokinetic parameters (Vmax, Km, Cl, t1/2)
Phenytoin
(Css) 2

Ludden method Mullen method ( orbit
graph)

Ludden method
Km phenytoin

-Km= ((SFMD1)-(SFMD2))/(((SFMD1))/Css1-(SFMD2)/Css2)

MD1 = 200 mg/day, Css1 = 8 mg/L

MD2 = 300 mg/day, Css2 = 20 mg/L
S = 0.92 ( capsules phenytoin Na)
F=1

-Km= ((0.921200 mg/day)-(0.921300 mg/day))/(((0.921200

mg/day))/(8 mg/L)-(0.921300 mg/day)/(20 mg/L))
-Km= (184 mg/day-276 mg/day)/(23L/day-13.8L/day) = (-92mg/day)/(9.2
L/day)=10 mg/L
Km phenytoin
Km = 10 mg/L Vmax
Vmax=(SFMD1)+Km(SFMD1/Css1)
Vmax=(0.921200 mg/day)+10 mg/L(0.921(200mg/day) / (8mg/L))
Vmax=414 mg/day
Cl phenytoin
phenytoin
Cl = Vmax/(Km+Css)
3.1 Km, Vd Css1 = 8 mg/L
Cl1 = (414 mg/day)/(10 mg/L +8 mg/L)=23 L/day
3.2 Km, Vd Css1 = 20 mg/L
Cl2 = (414 mg/day)/(10 mg/L +20 mg/L)=13.8 L/day
t1/2 phenytoin

phenytoin
t1/2 = ((0.693)Vd)/Cl

Vd Phenytoid 0.7 L/kg ( 68

kg)
4.1 Cl = 23 L/day, Css = 8 mg/L t1/2 =
((0.693)(0.7L/kg68kg))/(23 L/day)=1.43days

4.2 Cl = 13.8 L/day, Css = 20 mg/L t1/2 =

((0.693)(0.7L/kg68kg))/(13.8L/day)=2.39days
3. Phenytoin
15 mg/L

Phenytoin (:
Ludden method Mullen method)

Therapeutic range of phenytoin 10-20 mg/L

dosage regimen Css = 15 mg/L MD

(Cdesired = 12
mg/L)
MD= (Vmax Css)/(SF(Km+Css))
Km = 10 mg/L Vmax = 414 mg/day
Ludden method (Css = 12
mg/L) maintenance dose (MD)
MD= ((414 mg/day) 15 mg/L)/(0.921(10mg/L+15mg/L))
MD=
270 mg/day
Maintenance Dose
100 mg/cap
30 mg/cap ( 270 mg/day 300
mg/day (3 )

4 TDM of Carbamazepine

1 : 65 52

carbamazepine stroke 3
(average
steady-state plasma concentration) 6 mg/L


Pharmacokinetic parameter method

MD=(Cl Cav)/(SF)
MD=((0.064 L/kg52kg)6mg/L24hr/day)/(10.8)=599.04
mg/day600mg
(begin therapy) 1/4 1/3
MD 1/4 1/3 MD 7-14

immediate release cabamazepine 200 mg/tab

2,3
immediate release cabamazepine 200 mg/tab
2 : 2
carbamazepine 600 mg/day

4.5 mg/L
(average steady-state plasma concentration) 6
mg/L

Pharmacokinetic parameter method
Cl;

Cl

=
(SFDose/)/Cav
Cl =
(1 0.8 600mg/24hr)/(4.5mg/L)=4.44 L/hr
maintenance dose (MD)

New MD = (Clnew Cav)/(SF)

New MD = (4.44 L/hr6mg/L24hr/day)/(10.8)=
799.2mg/day800mg/day
Immediated release cabamazepine 200 mg/tap

MD 4 tablets/day