Drug Interactions During Anticonvulsant Therapy in Childhood: Diphenylhydantoin, Primidone, Phenobarbitone, Clonazepam, Nitrazepam, Carbamazepin and Dipropylacetate

Abstract

It is well known that the concomitant use of different drugs may alter the reactions of the body towards the individual components. This is particularly important in long-term anticonvulsant therapy which is frequently a combined therapy.

By carrying out statistical analysis of more than 6000 assays of the serum levels of anti-epileptic drugs an attempt was made to gain insight into the possible drug interactions. The following results were obtained:

1. There was an increase in serum levels of diphenylhydantoin when either clonazepam or dipropylacetate (short-term therapy) was given concomitantly.

2. There was a decrease in serum levels of diphenylhydantoin when carbamazepine, primidone or dipropylacetate (long-term therapy) were administered concomitantly.

3. There was an increase in the serum level of phenobarbitone when it was administered together with diphenylhydantoin.

4. There was an increase in the serum level of primidone when it was administered together with clonazepam.

5. There was a decrease in the serum level of primidone if it was administered concomitantly with either carbamazepine or dipropylacetate (long-term therapy).

Zusammenfassung

Es ist bekannt, daß die Kombination verschiedener Medikamente zu veränderten Reaktionen des Organismus den einzelnen Substanzen gegenüber führen kann. Interessant ist dies vor allem bei der antiepileptischen Therapie, da es sich um eine Langzeittherapie handelt und sehr häufig kombinierte Therapieregime durchgeführt werden. Aus über 6000 Messungen der Konzentration antiepileptischer Medikamente versuchten wir, anhand einer statistischen Analyse Aufschluß über mögliche Medikamentwechselwirkungen zu erhalten. Wir erzielten folgende Aussagen:

1. Anstieg der DPH-Serumkonzentrationen unter gleichzeitiger Gabe von Clonazepam und Dipropylacetat-Kurzzeit-Kombination,

2. Abfall der DPH-Serumkonzentrationen unter gleichzeitiger Gabe von Carbamazepin, höheren Primidondosen und Dipropylacetat-Langzeitkombination,

3. Anstieg der Phenobarbitalkonzentrationen unter DPH-Kombination,

4. Anstieg der Primidon-Serumkonzentrationen unter gleichzeitiger Clonazepam-Kombination,

5. Abfall der Primidonkonzentration unter Carbamazepin- und Dipropylacetat-Kombination.

Keyword

Drug interaction - anti-epileptic drugs - primidone - diphenylhydantoin - carbamazepin clonazepam - dipropylacetate - phenobarbitone