Frye M A, Kimbrell T A, Dunn R T, Piscitelli S, Grothe D, Vanderham E, Corá-Locatelli G, Post R M, Ketter T A
Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland 20892, USA.
J Clin Psychopharmacol. 1998 Dec;18(6):461-4. doi: 10.1097/00004714-199812000-00008.
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.
锂（Li）和加巴喷丁均仅通过肾脏排泄消除。联合使用时，考虑到锂的治疗指数较窄，竞争性药物相互作用可能会改变锂的肾脏排泄，具有重要的临床意义。本研究检测了13例接受安慰剂治疗然后接受稳态加巴喷丁（平均每日剂量：3646.15mg）的患者单次服用锂后的药代动力学特征。在两个阶段中，均口服单次600mg剂量的锂，并在0时、0.25、0.5、1、2、3、4、8、12、24、48和72小时获取系列锂水平。评估的药代动力学参数如下：锂的浓度-时间曲线下面积（AUC）、锂的最大浓度（Li Cmax）以及达到锂峰浓度的时间（Li Tmax）。接受加巴喷丁治疗的患者，72小时时锂的平均AUC为9.91±3.54mmol·hr/mL，与接受安慰剂治疗患者锂的平均AUC 10.19±2.89mmol·hr/mL相比，差异无统计学意义。加巴喷丁治疗组患者锂的平均Cmax为0.69±0.13mmol/L，与安慰剂组患者锂的平均Cmax 0.72±0.15mmol/L相比，差异无统计学意义。加巴喷丁治疗组患者血清锂的平均Tmax为1.38±0.62小时，与安慰剂组患者血清锂的平均Tmax 1.5±0.91小时相比，差异无统计学意义。这些数据表明，在这种高治疗剂量下，加巴喷丁治疗不会导致肾功能正常患者短期锂药代动力学发生具有临床意义的改变。这些初步数据需要在更大、更具异质性的患者样本中进行进一步的对照研究，并进行更长时间的评估，但它们确实提示这两种药物可联合用于双相情感障碍的治疗。
