表 1│Therapeutic ranges of blood levels and pharmacokinetics of major antiepileptic drugs
Maintenance dose a

Dose increase range

Adult（mg）

Child（mg/kg）

Adult（mg）

PB

30〜2002〜1030Primidone

PRM

750〜2,000

10〜25

Carbamazepine

CBZ

400〜1,200

5〜25

PHT

200〜300

3〜12

VPA

400〜1,200

15〜50

sustained release VPA-R

400〜1,200

15〜40

Generic name（abbreviation）

Phenobarbital

Phenytoinf

Valproate

Blood conc.
reference
range bChild（mg/kg） （μ g/mL）Child

70〜130almostunchanged

30〜75

0.5〜4

0.5〜2

5〜12

10〜20

3〜10

4.5〜11

2〜44〜64〜1210〜26 e

5〜12

8〜20

4〜83〜625〜50

1 〜3

7〜20

L：7〜42 almost L：2〜16
unchanged
H：20〜70
H：8〜304〜82〜6100〜200

5〜1050〜100

11〜20

6〜12

12〜26

15〜40

150〜200

0.025〜0.2

0.5〜1

Nitrazepam

NZP

5〜15

0.2〜0.5

2 〜5

0.1〜0.2

0.02〜0.1

CLB

5 〜7

40〜10010〜40

0.2〜1.0

5〜10

0.1〜0.2

0.03〜0.3

6〜15

2〜4

6〜12

7.5〜16

1〜3g

40〜60

20〜40

30〜40

1〜7

1〜4

0.015〜0.03 0.02〜（0.07） 17〜56

12〜46

22〜33

1〜41〜3h

KBr 1,500〜3,000

Adult3〜52〜6AZMChild

3 〜5

450〜1,000

Acetazolamide

withenzyme
inducer d250

CZP

Potassium bromide

monotherapy

100〜200

ESMCLB

Adult

15〜40

Clonazepam

N-desmethyl

T max：ch）
peak time（1〜2Ethosuximide

Clobazam

T 1/2：ch）
elimination half-life（

21〜40
17〜49

1.3〜2.5＜30〜16

0.5〜2

36〜46
250〜750

10〜20

125〜250

3 〜5

10〜14

10〜15

40〜70

200〜400

5〜10

750〜1,250

10〜13
days

2〜4
5〜8days

2
2〜3

1〜3

13〜20

1〜4

1〜3

Gabapentin

GBP

600〜2,400

5〜45

200〜400

5〜10

2〜20

5〜9

5 〜9Topiramate

TPM200〜600

4〜1025〜50

1〜2.5

5〜20

20〜30

12〜15

LTG

150〜400

1〜550〜100≦0.3

2.5〜15

15〜35

13〜27

1〜3.5

4〜5（1）combined with VPA

100〜200

1〜325〜50≦0.3

30〜9030〜70

4.8

3〜4.5

（2）combined with

200〜400

5〜1550〜100

≦1.2

8〜23

4〜11

1〜2

1.5〜3

150〜400

1〜525〜50

≦0.3

11〜50

7〜31

3.8

3.3

20〜60

250〜500

5〜10

5〜6

0.5〜2

Lamotrigineienzyme inducer d（3）combined with（1）and（2）

Levetiracetam

jRuﬁnamide

LEV 1,000〜3,000RFNkdepend onweightdepend on 200〜400weightStiripentol

STP 1,000〜2,500

20〜50

Vigabatrin

VGB50〜150

Perampanel
LacosamidemPERLCM

l500

l

4〜12

4〜12200〜400

200〜4002m

≦100

12〜46

6〜8

5 〜830〜40

8〜124 〜7

4〜6

10

4〜22

4〜13

≦50

2〜36

5〜84 〜60.5〜2

2

0.05〜0.4

53〜13625

0.25〜2

10〜20

12〜16

4

1〜2

0.5〜4

a： In children, the younger the age, the higher the dose per kg body weight is required to obtain a given blood concentration, the maintenance dose ishigher, and half-life and peak time are shorter. In adolescents, pharmacokinetics are almost the same as adults.
b： If eﬀective, blood concentration can stay low, or can be increased to higher than the therapeutic range as long as there is no adverse eﬀect.
c： This is the time for the concentration to decrease by half from the peak. The time until blood concentration decreases by one -half after administrationis peak time ＋ half-life. Half-life and peak time are in principle determined for monotherapy with drug taking after meal. In combination therapy,
half-life is shortened when the combination lowers blood level through interaction, and is prolonged when the combination increases blood concentration（see Interaction in CQ12‑4 on page 128）. Peak time is greatly shortened when drug is taken in fasting state, and is about 1.1-1.3 times
delayed for VPA sustained release preparation alone.
d： Enzyme-inducing drugs：PB, PRM, CBZ and PHT. Increase drug metabolism in the liver, concomitant use shortens half-life of original drug.
e： Value at the time when self-induction is completed（about 3-4 weeks after starting）.
f： For PHT, the higher the blood level, the longer is the half-life. L：low dose（blood level around 5 μ g/mL）, H：high dose（blood level 10 μ g/mL orabove）
g： Peak time of VPA sustained release preparation varies depending on the dosage form：5-10 h for Selenica ® R ﬁne granule, 7.5-10 h for Depakene ® Rtablet, and 13-16 h for Selenica ® R tablet.
h： N-DMCLB is a metabolite of CLB. N-DMCLB has anticonvulsive action of approximately 1/4 strength of that of CLB. When classified by CLB：
N-DMCLB concentration ratio into three groups of approximately 1：2-3（10% of the subjects）, around 1：10（80%）, and around 1：50-100（10%）, drowsiness occurs at a higher rate as the CLB：NDMCLB concentration ratio increases.
i： In Japan, monotherapy use is approved only for partial seizure（including secondarily generalized seizures）and tonic clonic seizure in 16 year-old andabove. To prevent rash（especially Stevens-Johnson syndrome）, follow the instructions in the package insert concerning the initial dose, the dose
increase range and the maximum dose of LTG.
j： Monotherapy use only for 4 year-old and above with partial seizure.
k： Covered by insurance for 4 year-old and above. Starting dose-maximum dose is as follows：15 to <30 kg in weight：200-1,000 mg, 30 to <50 kg：
400-1,800 mg, 50 to <70 kg：400-2,400 mg, ≥ 70 kg：400-3,200 mg. Dose increase range is：15 to <30 kg： ≤ 200 mg, and ≥ 30 kg： ≤ 400 mg.
Oﬃcial abbreviation is undecided and RUF is also commonly used.
l： Covered by insurance for 4 year-old and above. Oﬃcial abbreviation is undecided and PRP is also commonly used.
m： Covered by insurance for 16 year-old and above.
（Compiled from：Shorvon S, Perucca E, Engel J Jr, eds. The treatment of epilepsy, 4th edition. Chichester：Wiley Blackwell, 2015, p.376-700. / Wyllie E,Gidal BE, Goodkin HP, et al eds.：Wyllieʼs Treatment of Epilepsy：Principles and Practice, 6th edition. Philadelphia：Wolters Kluwer, 2015, p.593-768. /Patsalos PN, Bourgeois BFD：The Epilepsy Prescriberʼs Guide to Antiepileptic Drugs. Cambridge：Cambridge University Press, 2010. / Drugs in JapanForum, ed. Drugs in Japan：Ethical Drugs 2016 edition. Tokyo：Jiho Inc., 2015.）

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