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
