Warner Brad W, LaGrange Chad A, Tucker Tarvez, Bensalem-Owen Meriem, Pais Vernon M
University of Kentucky, Chandler Medical Center, Lexington, Kentucky 40536, USA.
Urology. 2008 Jul;72(1):29-32; discussion 32-3. doi: 10.1016/j.urology.2008.01.042. Epub 2008 Apr 24.
To provide prospective, longitudinal evidence of the effects of topiramate, an antiepileptic medication prescribed for migraine headaches, on stone-risk factors, specifically as pertaining to dosing and rapidity of onset.
Patients scheduled to begin topiramate therapy were recruited to participate in the study. Enrolled subjects collected a pretreatment 24-hour urine specimen with subsequent 24-hour urine specimens collected 5 days after beginning topiramate and after each dose escalation.
Six subjects enrolled in the study, 4 of whom completed two additional urine collections after initiating topiramate therapy. The pretreatment urine collections of the 4 subjects with additional samples revealed the following mean (range) values: urine volume 1550 (1300 to 1900) mL, pH 6.75 (6 to 7), creatinine 1436.3 (1196 to 1590) mg/day, calcium 305.8 (209 to 423) mg/day, and citrate 606.8 (290 to 860) mg/day. Five days after initiation of topiramate, mean calcium decreased to 211.5 mg/day (31% decrease), and mean citrate decreased to 398 (99 to 804) mg/day, an average decrease of 39.8% (6.5% to 65.9%) per patient. After a dose escalation, calcium increased to 286.8 mg/day, but citrate decreased further to 209 (119 to 353) mg/day, an average decrease of 65.1% (57.9% to 71.7%) per patient from pretreatment levels.
Topiramate therapy induces a profound decrease in urinary citrate levels, equivalent to the levels seen in distal renal tubular acidosis. Citrate levels decrease quickly after the start of topiramate therapy and continue to decrease with escalating doses.
提供前瞻性、纵向证据，以证明用于偏头痛治疗的抗癫痫药物托吡酯对结石风险因素的影响，特别是与给药剂量和起效速度相关的影响。
招募计划开始托吡酯治疗的患者参与本研究。入选的受试者收集一份治疗前24小时尿液样本，随后在开始托吡酯治疗5天后以及每次剂量增加后收集24小时尿液样本。
6名受试者入选本研究，其中4名在开始托吡酯治疗后完成了另外两次尿液收集。4名有额外样本的受试者治疗前尿液收集结果显示以下平均（范围）值：尿量1550（1300至1900）mL，pH值6.75（6至7），肌酐1436.3（1196至1590）mg/天，钙305.8（209至423）mg/天，枸橼酸盐606.8（290至860）mg/天。开始托吡酯治疗5天后，平均钙水平降至211.5mg/天（降低31%），平均枸橼酸盐水平降至398（99至804）mg/天，每位患者平均降低39.8%（6.5%至65.9%）。剂量增加后，钙水平升至286.8mg/天，但枸橼酸盐水平进一步降至209（119至353）mg/天，与治疗前水平相比，每位患者平均降低65.1%（57.9%至71.7%）。
托吡酯治疗可导致尿枸橼酸盐水平显著降低，与远端肾小管酸中毒时的水平相当。托吡酯治疗开始后枸橼酸盐水平迅速下降，并随着剂量增加持续下降。
