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 Cmax), and time to reach peak Li concentration (Li Tmax). 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 Cmax was 0.69+/-0.13 mmol/L for gabapentin patients and did not differ from the mean Li Cmax of 0.72+/-0.15 mmol/L for placebo patients. The mean serum Li Tmax was 1.38+/-0.62 hours for gabapentin patients and did not differ significantly from the mean serum Li Tmax 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.
Frye
M A
MA
Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland 20892, USA. maf@helix.nih.gov
Kimbrell
T A
TA
Dunn
R T
RT
Piscitelli
S
S
Grothe
D
D
Vanderham
E
E
Corá-Locatelli
G
G
Post
R M
RM
Ketter
T A
TA
D000085:Acetates / Q000494:pharmacology*; D000588:Amines; D018692:Antimanic Agents / Q000494:pharmacology*; D001714:Bipolar Disorder / Q000188:drug therapy / Q000378:metabolism*; D003509:Cyclohexanecarboxylic Acids; D003863:Depression / Q000188:drug therapy / Q000378:metabolism*; D004311:Double-Blind Method; D004347:Drug Interactions; D000077206:Gabapentin; D006801:Humans; D008094:Lithium / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008657:Metabolic Clearance Rate; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D018692:Antimanic Agents; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D008094:Lithium