Christensen Michael L, Mottern Robin K, Jabbour J T, Fuseau Eliane
Departments of Pharmacy and Pediatrics, Pediatric Pharmacology Research Unit, Center for Pediatric Pharmacokinetics and Therapeutics, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
J Clin Pharmacol. 2003 Jul;43(7):721-6.
Sumatriptan is a potent and selective vascular 5-HT1 receptor agonist effective for the treatment of migraine. In adults, intranasal sumatriptan is well absorbed and tolerated. The authors evaluated the pharmacokinetics and tolerability of a single dose of 20 mg intranasal sumatriptan in healthy adolescent migraineurs ages 12 to 17 years, administered outside of migraine attack. Serum sumatriptan levels were measured by high-performance liquid chromatography (HPLC) with electrochemical detection in serial samples collected over 8 hours. Physical exam, vital signs, clinical laboratory tests, and electrocardiogram measurements were monitored to assess safety and tolerability. A total of 16 subjects (10 males and 6 females) had pharmacokinetic data that could be analyzed, 2 withdrew from the study 30 and 60 minutes after dosing following the loss of venous access for blood sampling, and a bioanalysis failure resulted in loss of data from 3 subjects. Noncompartmental pharmacokinetic parameters (geometric mean and 95% confidence interval) for the remaining 16 subjects were as follows: Cmax was 13.9 (11.0, 17.6) ng/mL, AUC infinity was 57.3 (47.6, 69.0) ng/mL.h, and t1/2 was 2.0 (1.8, 2.3) hours. Population pharmacokinetic analysis for all subjects (n = 21) showed that clearance and volume of distribution increase slightly with age and body size, but the changes were minimal and would not warrant dose adjustment: CL/F was 316 L (coefficient of variance [CV] = 25%) and Vd/F was 1070 L (CV = 46%). Sumatriptan was well tolerated with only minor adverse events reported, which all resolved spontaneously. The pharmacokinetic parameters in these adolescent subjects were similar to those previously reported in adults, suggesting that adolescents should be dosed similar to adults.
舒马曲坦是一种强效且选择性的血管5-羟色胺1（5-HT1）受体激动剂，对偏头痛治疗有效。在成年人中，鼻内使用舒马曲坦吸收良好且耐受性佳。作者评估了单剂量20毫克鼻内舒马曲坦在12至17岁健康青少年偏头痛患者中的药代动力学和耐受性，给药时间为偏头痛发作之外。通过高效液相色谱法（HPLC）及电化学检测，在8小时内采集的系列样本中测量血清舒马曲坦水平。监测体格检查、生命体征、临床实验室检查及心电图测量，以评估安全性和耐受性。共有16名受试者（10名男性和6名女性）有可分析的药代动力学数据，2名受试者在给药后30分钟和60分钟因采血失去静脉通路而退出研究，3名受试者因生物分析失败导致数据缺失。其余16名受试者的非房室药代动力学参数（几何均值和95%置信区间）如下：Cmax为13.9（11.0，17.6）纳克/毫升，AUC无穷大为57.3（47.6，69.0）纳克/毫升·小时，t1/2为2.0（1.8，2.3）小时。对所有受试者（n = 21）的群体药代动力学分析表明，清除率和分布容积随年龄和体型略有增加，但变化极小，无需调整剂量：CL/F为316升（变异系数[CV] = 25%），Vd/F为1070升（CV = 46%）。舒马曲坦耐受性良好，仅报告了轻微不良事件，且均自发缓解。这些青少年受试者的药代动力学参数与先前在成年人中报告的相似，表明青少年的给药方式应与成年人相似。
