Kinetic effects of multiple oral doses of acetaminophen on a single oral dose of lamotrigine

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Abstract
In this double-blind, randomized, crossover, placebo-controlled study, the effect of multiple oral doses of acetaminophen on lamotrigine disposition was examined in healthy volunteers. Eight volunteers received two single 300 mg oral doses of lamotrigine, administered 20 days apart. Acetaminophen (2.7 gm/day) or placebo was taken for 24 hours before and continued for 10 days after such lamotrigine dose. Area under the plasma concentration-time curve for lamotrigine [AUC(0-.infin.)] and lamotrigine half-life were statistically decreased by 20% (229.0 .+-. 62.5 .mu.g .cntdot. hr/ml versus 191.2 .+-. 42.1 .mu.g .cntdot. hr/ml, p < 0.01) and 15% (35.7 .+-. 9.3 hours versus 30.2 .+-. 7.3 hours, p < 0.01), respectively, when concurrently administered with acetaminophen. There was no significant difference in the peak plasma concentration or the time to reach peak plasma concentration. The percentage of the dose of lamotrigine recovered in the urine (total) was significantly higher during the acetaminophen treatment (65.9% .+-. 12.3% versus 72.5% .+-. 5.7%, p = 0.048). Acetaminophen seems to facilitate lamotrigine removal through a yet to be determined mechanism(s).