Pharmacokinetic Interactions Between Lamotrigine and Other Antiepileptic Drugs in Children with Intractable Epilepsy

Epilepsia - Tập 37 Số 8 - Trang 769-773 - 1996
Ann-Sofie Eriksson1, Kalle Hoppu, Arne Nergårdh, Lars O. Boréus
1Department of Clinical Pharmacology, Karolinska Hospital, Stockholm, Sweden

Tóm tắt

Summary: Purpose: We wished to determine the oral pharmacokinetics of lamotrigine LTG and to assess possible interactions with other AEDs in an unselected population of children. Concentration data in plasma and in CSF for lamotrigine as well as for the other AEDs are presented. Methods: Thirty‐one children, children and young adults aged > 2 years with intractable generalized epilepsy despite adequate duration and dose of at least three conventional AEDs were studied. Results: There was a linear relation between the dose administered and the maximal plasma concentration, indicating that saturation of absorption or elimination mechanisms did not occur in the dose range studied. The median elimination half‐life (t1/2) in patients receiving concomitant valproate (VPA) was 43.3 h; in patients receiving carbamazepine (CBZ) and/or phenobarbital (PB), it was 14.1 h; and in patients receiving both VPA and CBZI PB or other antiepileptic drugs (AEDs), it was 28.9 h. No clinically important changes in the plasma levels of CBZ, VPA, valproate, ethosuximide, or PB were observed in the follow‐up period (2–12 months). No dose adjustments of concomitant AEDs were necessary. The plasma concentration of clonazepam (CZP) was reduced when LTG was introduced. Conclusions: The complex interaction between LTG and other AEDs in children with intractable epilepsy makes therapeutic drug monitoring (TDM) desirable.

Từ khóa


Tài liệu tham khảo

10.1016/0920-1211(92)90065-2

10.1111/j.1528-1157.1986.tb03573.x

Posner J, 1991, Comparison of lamotrigine pharmacokinetics in young and elderly healthy volunteers, J Pharm Med, 1, 121

10.1038/clpt.1987.193

10.1016/0920-1211(87)90041-6

10.1111/j.1528-1157.1986.tb03536.x

10.1016/0920-1211(91)90012-5

10.1111/j.1365-2125.1992.tb04079.x

10.1111/j.1528-1157.1985.tb05417.x

Forssblad E, 1995, Liquid chromato‐graphic determination of plasma lamotrigine in pediatric samples, J Pharm Biomed Analysis, 00, 00

YauMK WarginWA.Single‐dose and steady‐state pharmacokinetic study of lamictal in healthy male volunteers. Wellcome Internal Report no. THRS/90/0024.

Wallace SJ., 1990, Add‐on open trial of lamotrigine in resistant child seizures, Brain Dev, 12, 734

ReyE VauzelleF PonsG et al.Pharmacokinetics of lamotrigine in young epileptic children.Presented at the 5th World Confernece on Clinical Pharmacology and Therapeutics Yokohama Japan 1992:154.

Yuen WC, 1988, Lamotrigine pharmacokinetics: oral and i.v. infusion in man, Br J Clin Pharmacol, 26, 00

Thông tin
Thông tin xuất bản

Epilepsia

Tập 37 Số 8

769-773

Thông tin tác giả