Pharmacokinetics of lamotrigine (Lamictal) in plasma and saliva

The kinetics of lamotrigine (LTG) disposition in plasma and saliva was evaluated in patients undergoing long-term antiepileptic drug therapy. Blood and saliva samples were collected simultaneously at intervals during the study and the concentration of LTG was measured by HPLC. Concentrations of LTG in saliva were proportional to plasma LTG concentrations, with a significant (p) correlation of r = 0.95 + 0.18. The saliva concentration-time curves of LTG were parallel to those derived for plasma LTG. The kinetics of LTG absorption, elimination and mean residence time were identical in both saliva and plasma estimations. The saliva/plasma ratio, determined from the terminal phase of individual patient LTG concentration vs time curves, was used to predict plasma LTG concentrations from saliva determinations. The binding of LTG to plasma proteins remained constant in patients treated with sodium valproate and/or enzyme-inducing drugs. Thus, LTG determination in saliva represents a noninvasive alternative for therapeutic drug monitoring and may also be employed for studying LTG pharmacokinetics.