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Arzneimittelforschung 2010; 60(7): 421-426
DOI: 10.1055/s-0031-1296306
CNS-active Drugs · Hypnotics · Psychotropics · Sedatives
Editio Cantor Verlag Aulendorf (Germany)

Effects of charcoal on the absorption and elimination of the antiepileptic drugs lamotrigine and oxcarbazepine

Tapani Keränen
1   Department of Pharmacy, University of Eastern Finland, Kuopio, Finland
2   Medical School, University of Tampere, Finland
,
Annamari Sorri
2   Medical School, University of Tampere, Finland
,
Eeva Moilanen
2   Medical School, University of Tampere, Finland
3   Department of Clinical Chemistry, Tampere University Hospital, Tampere, Finland
,
Pauli Ylitalo
2   Medical School, University of Tampere, Finland
3   Department of Clinical Chemistry, Tampere University Hospital, Tampere, Finland
› Author Affiliations
Further Information

Publication History

Publication Date:
03 December 2011 (online)

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Abstract

Objective:

The effects of single and repeated doses of oral activated charcoal (OAC) on the absorption and elimination of the antiepileptic drugs, lamotrigine (CAS 84057-84-1, LTG, Lamictal™) and oxcarbazepine (CAS 28721-07-5, OXC, Trileptal™) were studied in healthy volunteers to assess the therapeutic potential of OAC in the treatment of LTG and OXC overdose.

Methods:

In three open, randomized, cross-over sessions with ≥14 days wash-out, LTG 100 mg and OXC 600 mg were given orally, each to 6 subjects. In one session the drugs were given alone, and in two others with single (50 g) or repeated (20 g) doses of OAC as water suspension. The single OAC dose was given 30 min after the drugs, and repeated doses 6–72 h after LTG and 12–48 h after OXC. Serumconcentrations of the parent drugs as well as those of the pharmacolocigally active metabolite of OXC, 10,11-dihydro-10-hydroxy-carbamazepine (MHD), were measured with reverse-phase highper-formance liquid chromatography. Pharmacokinetic variables were calculated by non-compartmental analysis.

Results:

Single OAC dose decreased AUC0–∞ of LTG, OXC and MHD to 58%, 2.8% and 4.2% of the respective variables without OAC. Also T max of OXC and MHD decreased to 4.4% and 8.1%, respectively. Repeated OAC doses after LTG decreased its AUC from 6 h to infinity (AUC6–∞) to 39% and t1/2β to 44%. Repeated OAC doses after a single dose of OXC decreased the AUC12–∞ and t1/2β of MHD to 46% and 45% of the respective variables without OAC.

Conclusion:

OAC greatly reduces gastrointestinal absorption of LTG and especially that of OXC, and it accelerates the elimination of LTG and MHD. The use of OAC is hence strongly favoured in the treatment of overdose with these drugs.

Key words

Antiepileptic drugs - CAS 28721-07-5 - CAS 84057-84-1 - Lamotrigine, overdose, pharmacokinetics - Oral activated charcoal - Oxcarbazepine, overdose, pharmacokinetics
 

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