The effect of parenteral imipramine on the oral absorption of lamotrigine in rats

Abstract

The interaction between imipramine and lamotrigine was investigated following the acute administration of lamotrigine (20 mg kg−1, p.o.) alone or together with imipramine (25 mg kg−1, i.p.) to rats. Similarly, the same doses of lamotrigine alone or when they were given together with imipramine (15 mg kg−1, i.p.) were administered to rats chronically for 5 days. Plasma samples were collected at 0.25, 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0 and 24.0 h after lamotrigine administration. An assay of lamotrigine in plasma was performed using a high-performance liquid chromatographic (HPLC) method. The concomitant administration of imipramine (25 mg kg−1, i.p) with lamotrigine (20 mg kg−1, p.o.) acutely, resulted in a significant (P<0.05) decrease in the maximum plasma concentration (Cmax), the mean area under the plasma concentration–time curve (AUC) and the half-life (t1/2), and a significant decrease (P<0.001) in the time to reach maximum concentration (tmax), as compared to those obtained for lamotrigine alone. Similarly, the chronic administration of imipramine together with lamotrigine lead to significant decreases in Cmax, AUC and t1/2 while the tmax remained unchanged. These results suggest that a significant decrease in the absorption of lamotrigine occurs when it is given acutely or chronically together with the antidepressant imipramine.