Pharmacokinetics of sumatriptan nasal spray in adolescents
Pharmacokinetics of sumatriptan nasal spray in adolescents
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DOI：
10.1177/0091270003254638
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发表时间：
2003-07-01
影响因子：
2.9
通讯作者：
Fuseau, E
中科院分区：
文献类型：
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作者：
Christensen, ML;Mottern, RK;Fuseau, E
舒马曲坦是一种强效且选择性的血管5 - HT1受体激动剂，对偏头痛的治疗有效。在成年人中，鼻内给予舒马曲坦吸收良好且耐受性佳。作者评估了在12至17岁健康青少年偏头痛患者中，在偏头痛发作间期给予单次20mg鼻内舒马曲坦的药代动力学和耐受性。通过高效液相色谱（HPLC）结合电化学检测，对8小时内采集的系列样本测定血清舒马曲坦水平。监测体格检查、生命体征、临床实验室检查和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分钟因采血静脉通路丧失而退出研究，3名受试者因生物分析失败导致数据丢失。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）ng/mL，AUC（∞）为57.3（47.6，69.0）ng/mL·h，t1/2为2.0（1.8，2.3）小时。对所有受试者（n = 21）进行的群体药代动力学分析显示，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 L（变异系数[CV] = 25%），Vd/F为1070 L（CV = 46%）。舒马曲坦耐受性良好，仅报告有轻微不良事件，且均自行缓解。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道的相似，表明青少年的给药剂量应与成年人相似。
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: C-max was 13.9 (11.0,17.6) ng/mL, AUC(infinity) was 57.3 (47.6, 69.0) ng/mL(.)h, and t(1/2) 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: CLIF 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.