Akademik Veri Yönetim Sistemi
ARZNEIMITTEL-FORSCHUNG-DRUG RESEARCH, cilt.57, sa.8, ss.517-521, 2007 (SCI-Expanded)
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 (r(2) = 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 (TM). Plasma t(1/2) and MRT were not significantly different from those found from saliva. The mean values of lamotrigine peak saliva concentrations (C,.), areas under the curve of concentration versus time from zero to infinity (AUC(0 ->infinity)), end areas under the curves of the product of time and concentration versus time from zero to infinity (AUM(0 ->infinity)) 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.