Lamotrigine, a new anticonvulsant: pharmacokinetics in normal humans.
The pharmacokinetics of lamotrigine, a new anticonvulsant, were studied in three studies in normal volunteers. In the first study, five subjects received oral doses of lamotrigine up to 240 mg. A linear relationship was observed between dose administration and both peak drug concentration and AUC. In a second study 10 subjects received 120 mg lamotrigine and the mean (+/- SD) of the elimination half-life (t1/2) was 24.1 +/- 5.7 hours and of volume of distribution/bioavailability 1.2 +/- 0.12 L/kg. Saliva concentrations were 46% of the plasma concentration. Total urinary recovery of drug over 144 hours was 70.5% of the oral dose. A glucuronide conjugate accounted for 89.4% of the urinary recovery. In a third study the kinetics of repeated administration were studied. Fifteen subjects were randomized to lamotrigine (n = 10) or placebo (n = 5) and received multiple doses over 7 days. The overall plasma elimination t1/2 calculated from data during the 7 days was 25.5 +/- 10.2 hours. Observed pharmacokinetics on multiple administration obeyed closely those predicted from the single-dose experiment, suggesting the absence of autoinduction of metabolism. No clinically important side effects or changes in central nervous system or cardiovascular system variables, hematology, biochemistry, or urinalysis occurred during the 7 days.
Cohen
A F
AF
Clinical and Applied Research Division, Wellcome Research Laboratories, Beckenham, Kent, UK.
Land
G S
GS
Breimer
D D
DD
Yuen
W C
WC
Winton
C
C
Peck
A W
AW
D000927:Anticonvulsants / Q000009:adverse effects / Q000032:analysis / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006207:Half-Life; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D011897:Random Allocation; D012463:Saliva / Q000378:metabolism; D013997:Time Factors; D014227:Triazines / Q000009:adverse effects / Q000032:analysis / Q000493:pharmacokinetics*
D000927:Anticonvulsants; D014227:Triazines; D000077213:Lamotrigine