ANTICONVULSANTS

Anticonvulsants: Indications and Pharmacokinetics

Drug

Labeled indications

Protein
binding (%)

Metabolism/Excretion

t (h)

Therapeutic serum
levels (mcg/mL)

53 to 140

15 to 40

Dosedependentb

5 to 20

95 (active metabolite)

nd

3 to 9c

15 to 50

Phenobarbitala
(PB)

Status epilepticus Epilepsy, all forms Tonic-clonic

Phenytoin

Tonic-clonic Psychomotor

90

Liver; renal excretion. < 5% excreted unchanged

Mephenytoin

Tonic-clonic Psychomotor Focal Jacksonian

nd

Liver

Ethotoin

Tonic-clonic Psychomotor

nd

Liver; renal excretion of metabolites

Ethosuximide

Absence

Liver; 25% excreted unchanged in urine

30 (children 7 to 9 yrs) 40 to 60
(adults)

40 to 100

Methsuximide

Absence

nd

Liver; < 1% excreted unchanged in urine

<2 (40, active metabolite)

nd

Phensuximide

Absence

nd

Urine, bile

8 (active metabolite)

nd

Zonisamide

Partiald

40

Accetylation and reduction; excreted in urine

63

nd

Oxazolidinedione Trimethadione
s

Absence

Demethylated to dimethadione; 3% excreted unchanged

6 to 13 days (dimethadione)

700 (dimethdione)

Benzodiazepines Clonazepam

Absence Myoclonic Akinetic

Barbiturates

Hydantoins

Succinimides

Sulfonamides

Clorazepate

Partiald

40 to 60

Liver; 25% eliminated unchanged in urine

50 to 85

5 metabolites identified; urine is major excretion route

18 to 60

20 to 80 ng/mL

97

Hydrolyzed in stomach to desmethyldiazepam (active);

30 to 100

nd

metabolized in liver, renally excreted

Diazepam

Status epilepticusd Epilepsy, all formsd

97 to 99

Liver, active metabolites

Primidone

Tonic-clonic Psychomotor Focal

20 to 25

Metabolized to PB and PEMA, both active

Valproic acid

Absence

80 to 94

Liver; excreted in urine

Carbamazepine Tonic-clonic Mixed Psychomotor

Miscellaneous

Phenacemide

Severe mixed psychomotor

Felbamatef

Partial (adults) Partial/generalized assoc. with

Lennox-Gastaut syndrome (children)

Oxcarbazepine

Partial

Lamotrigine

Partial (adults)

75

nd

22 to 25

20 to 50

nd

5 to 15 (primidone) 10 to 18
(PEMA) 53 to 140 (PB)

5 to 12 (primidone) 15 to
40 (PB)

5 to 20

50 to 150

Liver to active 10, 11-epoxide. 72% excreted in urine, 28% 18 to 54 (initial) 10 to 20e 6 (10,
in feces
11-epoxide)

Liver

40% to 50% unchanged in urine, 40% as unidentified

metabolites and conjugates

4 to 12

nd

nd

20 to 23

ndg

40

Reduced to 10-monohydroxy metabolite (active); excreted

in urine (80%)

2; 9 (MHD)

ndg

55

Glucuronic acid conjugation to inactive metabolites; 94%

excreted in urine, 2% in feces

33e

nd

Other barbiturates are also used as anticonvulsants. See Sedatives/Hypnotics section.

Exhibits dose-dependent, nonlinear pharmacokinetics.

Below 8 mcg/mL; > 8 mcg/mL, t not defined because of dose-dependent, nonlinear pharmacokinetics.

Recommended for adjunctive use.

Undergoes autoinduction. Half-life after repeated doses.

Because of cases of aplastic anemia, it has been recommended that the use of this drug be discontinued unless, in the judgment of the physician, continued therapy is warranted.

Value of monitoring blood levels not established.