Wilting Ingeborg, Movig Kristian Ll, Moolenaar Marieke, Hekster Yechiel A, Brouwers Jacobus Rbj, Heerdink Eibert R, Nolen Willem A, Egberts Antoine Cg
Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Bipolar Disord. 2005 Jun;7(3):274-80. doi: 10.1111/j.1399-5618.2005.00199.x.
Lithium is a drug with a narrow therapeutic window. Concomitantly used medication is a potentially influencing factor of lithium serum concentrations. We conducted a multicentre retrospective case-control study with the aim of investigating lithium-related drug interactions as determinants of elevated lithium serum levels in daily clinical practice.
Cases were patients with an increase of at least 50% in lithium serum concentrations resulting in an elevated lithium serum level of at least 1.3 mmol/L, and who were not suspected of a suicide attempt. Controls were patients who showed stable lithium serum levels within the therapeutic range. Use and start of non-steroidal anti-inflammatory drugs, diuretics, renin-angiotensin inhibitors, theophyllin and antibiotics were investigated as potential determinants of the elevated lithium serum levels. Irregularity in lithium dispensing pattern, change in lithium dosing regimen, age, gender, prescribing physician and laboratory parameters were investigated as potential confounders.
We included 51 cases and 51 controls in our study. Five (9.8%) controls and 15 (29.4%) cases used potentially interacting co-medication [OR of 3.83 (95%CI 1.28-11.48)]. Start of potentially interacting co-medication was observed in eight (15.7%) cases and in zero (0%) controls resulting in an OR of 20.13 (95% CI 1.13-359). After adjustment for co-medication, irregularity in lithium dispensing pattern, change in lithium dosing regimen, and age, the statistically significant association was lost. We report an OR of 2.70 (95% CI 0.78-9.31) for use of concomitant medication, with a large contribution of antibiotic agents, and an OR of 3.14 (95% CI 1.15-8.61) for irregularity in lithium dispensing pattern.
Use of co-medication, especially antibiotics, tends to be associated with elevated lithium serum levels.
锂是一种治疗窗狭窄的药物。同时使用的药物是影响锂血清浓度的一个潜在因素。我们开展了一项多中心回顾性病例对照研究，旨在调查在日常临床实践中，锂相关药物相互作用作为锂血清水平升高的决定因素。
病例为锂血清浓度至少升高50%，导致锂血清水平至少达到1.3 mmol/L且未怀疑有自杀企图的患者。对照为锂血清水平在治疗范围内保持稳定的患者。研究了非甾体抗炎药、利尿剂、肾素 - 血管紧张素抑制剂、茶碱和抗生素的使用及起始使用情况，将其作为锂血清水平升高的潜在决定因素。研究了锂给药模式的不规律、锂给药方案的改变、年龄、性别、开处方医生和实验室参数作为潜在混杂因素。
我们的研究纳入了51例病例和51例对照。5例（9.8%）对照和15例（29.4%）病例使用了可能相互作用的联合用药[比值比为3.83（95%置信区间1.28 - 11.48）]。在8例（15.7%）病例中观察到开始使用可能相互作用的联合用药，而对照中为0例（0%），比值比为20.13（95%置信区间1.13 - 359）。在对联合用药、锂给药模式的不规律、锂给药方案的改变和年龄进行调整后，统计学上的显著关联消失。我们报告联合用药的比值比为2.70（95%置信区间0.78 - 9.31），其中抗生素的影响较大，锂给药模式不规律的比值比为3.14（95%置信区间1.15 - 8.61）。
联合用药，尤其是抗生素的使用，往往与锂血清水平升高有关。
