Carbamazepine: An Attempt to Correlate Serum Levels with Anti-Epileptic and Side Effects

Schneider, Helga

doi:10.1007/978-3-642-85921-2_14

Cited by 19 publications

(11 citation statements)

References 4 publications

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“…Nystagmus was present in an appreciable number of his patients with serum carbamazepine levels of 1.5J.1g/ml. These observations are puzzling and are in contrast to Schneider (1975), who noted the first appearance of side-effects beyond a threshold of 8.9J.1g/mi.…”

Section: Relation Of Activity To Plasma Levelcontrasting

confidence: 71%

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Clinical Pharmacokinetics of Anticonvulsants

Hvidberg

Dam

1976

Clinical Pharmacokinetics

141

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Anticonvulsant therapy was among the first areas to benefit from clinical pharmacokinetic studies. The most important advantage is that the frequent interindividual variation in the plasma level/dose ratio for these drugs can be circumvented by plasma level monitoring. For several anticonvulsants the brain concentration is shown to parallel the plasma concentration. Phenytoin (diphenylhydantoin) is stil the most important anticonvulsant and the one for which kinetics have been thoroughly investigated in man. These investigations have revealed several reasons for the wellknown difficulties in using this drug clinically. The absorption rate and fraction are very much dependent on the pharmaceutical preparation, and changes of brand may alter the plasma level of phenytoin in spite of unaltered dose. The elimination capacity is saturable causing dose dependent kinetics, which again means disproportional changes in plasma level with changes in dose. Great individual variations exist in the rate of metabolism, and several pharmacokinetic drug interactions are known. As an optimum therapeutic plasma concentration range has been established monitoring plasma levels must be strongly advocated. Interpretation of plasma levels in uraemic patients must take into account decreased protein binding of the drug. Carbamazepine is probably as effective as phenytoin. The elimination is a first order process, but the rate of metabolism increases after a few weeks' treatment. An active metabolite (epoxide) may be the cause of some side-effects. Combined treatment with other anticonvulsant drugs decreases the half-life and more frequent dosing may be necessary. An optimum therapeutic concentration range has been suggested and plasma monitoring is advocated, along with that of the active metabolite, the epoxide. Phenobarbitone is still much used but its kinetics have been investigated to a lesser extent. The main problem is the variability in the rate of elimination. In children the half-life of phenobarbitone is only half of that in adults. An optimum therapeutic plasma range has been established and monitoring is recommended. Primidone may have an anticonvulsant activity in itself, but its main metabolite is phenobarbitone. The relatively rapid elimination of primidone is offset by the long half-life of phenobarbitone. An optimum therapeutic range has been suggested, but plasma level monitoring must include determination of phenobarbitone. Ethosuximide. The clinical pharmacokinetics of this important petit mal anticonvulsant is not well known. It has a relatively long half-life (in adults 2 to 3 days; in children shorter). An optimum therapeutic range has been suggested, and routine monitoring of plasma levels may be recommended. Diazepam exerts a repid anticonvulsant activity when the plasma concentration exceeds approximately 500ng/ml after intravenous injection. The kinetic pattern is complex in man. Clonazepam. The clinical pharmacokinetics are still not fully investigated but a therapeutic range has been suggested...

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Section: Relation Of Activity To Plasma Levelcontrasting

confidence: 71%

“…These authors were not able to define any therapeutic level for psychomotor seizures. Schneider (1975) found in institutionalised patients, good seizure control on an average of 4.6 ± 1.3J.lg/ml and in hospitalised patients 6.5 ± 3. OJ.lg/ml , both fasting serum levels.…”

Section: Relation Of Activity To Plasma Levelmentioning

confidence: 97%

Clinical Pharmacokinetics of Anticonvulsants

Hvidberg

Dam

1976

Clinical Pharmacokinetics

141

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“…The dose given in the present study was about equal to the dosage used in other studies [4,11,13]. In the treat ment of epilepsy, the therapeutic zone is 4-10 pg/ml [14,16].…”

Section: Discussionmentioning

confidence: 99%

“…In a study on the side effects of carbamazepine, neurological side effects such as headache, diplopia, and tiredness were found to be as sociated with high serum levels (ca. 11 pg/ml) [16]. Although reports of hematologic toxic ity are rare [15], this effect is important in view of the serious consequences of bonemarrow depression.…”

Section: Discussionmentioning

confidence: 99%

The Value of Carbamazepine in the Treatment of Tinnitus

Hulshof¹,

Vermeij

1985

ORL

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“…Methods are now available for measuring serum levels of the drug (Meijer, 1971;Christiansen, 1973). In most studies dealing with serum levels and seizure control, carbamazepine was added to other anticonvulsant drugs (Parsonage, 1972;Schneider, 1975;Monaco et al, 1976).…”

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confidence: 99%