Abstract
The relationship between lamotrigine (CAS 84057-84-1) concentrations in saliva and plasma in healthy volunteers were examined, as well as the possibility of using
saliva to monitor levels for effective therapy. The study was performed with 14 healthy
volunteers, mean age 23 ± 2 (SD) years. After single oral doses of 200 mg, plasma
and stimulated saliva samples were collected simultaneously at 0, 0.25, 0.5, 1, 2,
4, 6, 8, 10, 12, 24, 48, 72 and 96 h. The pH values of saliva samples were recorded.
Lamotrigine concentrations were determined by a validated HPLC method. Fraction of
drug bound to plasma proteins was calculated mathematically by the modified Henderson-Hasselbalch
equation. Linear regression was used to evaluate the correlations. The remnant of
orally administered drug contaminated the saliva samples and gave spuriously high
values for up to 2 h, which were omitted. There was significant correlation (r2 = 0.677, p < 0.0001) between plasma and saliva concentrations from 2–96 h after administration.
The mean ratio of saliva to plasma concentration was 0.426 ± 0.153 (mean ± SD). Protein
binding, calculated from the concentrations in saliva was 57.5 ±15.1 % (mean ± SD).
Noncompartmental analysis was conducted with the program Kinetica™. Plasma t1/2 and MRT were not significantly different from those found from saliva. The mean values
of lamotrigine peak saliva concentrations (Cmax), areas under the curve of concentration versus time from zero to infinity (AUC0→∞), and areas under the curves of the product of time and concentration versus time
from zero to infinity (AUMC0→∞) were proportionally lower than in plasma. The results support the use of saliva
concentration as a convenient, painless and noninvasive alternative to plasma for
monitoring lamotrigine therapy.
Key words
Antiepileptics - CAS 84057-84-1 - Drug monitoring - Lamotrigine, pharmacokinetics,
plasma-saliva concentration correlation
