Twelve healthy volunteers (group A) received raltegravir (400 mg twice daily, fasting) from days 1 to 5 with a single dose of lamotrigine (100 mg) on day 4. After a washout period, participants received a second single dose of lamotrigine (100 mg) without raltegravir (day 32). In group B, 12 participants received the same treatment as in group A but in reverse order. AUCs (0-48 h) were determined for lamotrigine and lamotrigine-2N-glucuronide on days 4 and 32. AUCs (0-8 h) were determined for raltegravir when coadministered with lamotrigine. There was no significant effect of raltegravir on lamotrigine AUC (1% decrease) and Cmax (6% decrease). The mean ratio of the AUCs of lamotrigine-2N-glucuronide to lamotrigine was similar when lamotrigine was taken alone (0.35) or when taken with raltegravir (0.36). Raltegravir pharmacokinetics were similar to historical controls, indicating no significant effect of a single dose of lamotrigine on raltegravir. It was observed that raltegravir AUC displayed large interindividual variability (CV=77%) and possible diurnal variation (morning trough concentrations were 3 to 4-fold higher than at 8 h post dose).
The effect of raltegravir on the glucuronidation of lamotrigine. van Luin M, Colbers A, Verwey-van Wissen CP, et al. J Clin Pharmacol, 2009, 49(10): 1220-1227.