Gabapentin does not alter single-dose lithium pharmacokinetics

Lithium (Li) and gabapentin are both exclusively eliminated by renal excretion. When used in combination, a competitive drug-drug interaction could possibly alter Li renal excretion with important clinical implications considering the rather narrow therapeutic index of Li. This study examined the single-dose pharmacokinetic profiles of Li in 13 patients receiving placebo and then steady-state gabapentin (mean daily dose: 3,646.15 mg). During both phases, a single 600-mg dose of Li was orally administered with serial Li levels obtained at time zero and at 0.25, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, and 72 hours. The pharmacokinetic parameters assessed were the following: area under the concentration time curve (AUC) for Li, maximal concentration of Li (Li C-max), and time to reach peak Li concentration (Li T-max). For patients receiving gabapentin, the mean Li AUC at 72 hours was 9.91 +/- 3.54 mmol x hr/mL and did not differ significantly from the mean Li AUC of 10.19 +/- 2.89 mmol x hr/mL for patients receiving placebo. The mean Li C-max was 0.69 +/- 0.13 mmol/L for gabapentin patients and did not differ from the mean Li C-max of 0.72 +/- 0.15 mmol/L for placebo patients. The mean serum Li T-max was 1.38 +/- 0.62 hours for gabapentin patients and did not differ significantly from the mean serum Li T-max of 1.5 +/- 0.91 hours for placebo patients. These data indicate that gabapentin treatment at this high therapeutic dose does not cause clinically significant alterations in short-term Li pharmacokinetics in patients with normal renal function. These preliminary data warrant further controlled study in a larger, more heterogenous patient sample and a longer duration of assessment, but they do suggest that these two medications may be administered in combination for the management of bipolar disorder.