Effects of charcoal on the absorption and elimination of the antiepileptic drugs lamotrigine and oxcarbazepine.
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 > or = 14 days washout, 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. Serum concentrations 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 high-performance liquid chromatography. Pharmacokinetic variables were calculated by non-compartmental analysis.


RESULTS
Single OAC dose decreased AUC0-infinity of LTG, OXC and MHD to 58%, 2.8% and 4.2% of the respective variables without OAC. Also Tmax 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-infinity) to 39% and t1/21beta to 44%. Repeated OAC doses after a single dose of OXC decreased the AUC12-infinity and t/12beta of MHD to 46% and 45% of the respective variables without OAC.


CONCLUSIONS
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.
Keränen
Tapani
T
Department of Pharmacy, University of Eastern Finland, Kuopio, Finland. tapani.keranen@uef.fi
Sorri
Annamari
A
Moilanen
Eeva
E
Ylitalo
Pauli
P
D000284:Administration, Oral; D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002220:Carbamazepine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D002606:Charcoal / Q000494:pharmacology* / Q000627:therapeutic use; D018592:Cross-Over Studies; D005260:Female; D006207:Half-Life; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D000077213:Lamotrigine; D008297:Male; D000078330:Oxcarbazepine; D014227:Triazines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055815:Young Adult
D000927:Anticonvulsants; D014227:Triazines; D002606:Charcoal; D002220:Carbamazepine; D000077213:Lamotrigine; D000078330:Oxcarbazepine