Lisdexamfetamine Dimesylate: Linear Dose-Proportionality, Low Intersubject and Intrasubject Variability, and Safety in an Open-Label Single-Dose Pharmacokinetic Study in Healthy Adult Volunteers

被引:56
作者
Ermer, James [1 ]
Homolka, Robert [1 ]
Martin, Patrick [1 ]
Buckwalter, Mary [1 ]
Purkayastha, Jaideep [1 ]
Roesch, Benno [2 ]
机构
[1] Shire Dev, Wayne, PA 19087 USA
[2] Adv Biomed Res, Hackensack, NJ USA
关键词
Lisdexamfetamine dimesylate; Vyvanse; attention-deficit/hyperactivity disorder; pharmacokinetics; dose escalation; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DOUBLE-BLIND; EXTENDED-RELEASE; CHILDREN; METHYLPHENIDATE; PHARMACOTHERAPY; EFFICACY; MISUSE; ADHD;
D O I
10.1177/0091270009357346
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The pharmacokinetics of lisdexamfetamine dimesylate, a long-acting prodrug stimulant, and its active moiety, d-amphetamine, including dose-proportionality and variability, were assessed in 20 healthy adults. Subjects received a single dose, sequentially, of 50, 100, 150, 200, and 250 mg of lisdexamfetamine dimesylate. Plasma lisdexamfetamine dimesylate and d-amphetamine were measured before dosing and 0.25 to 96 hours postdose. Dose-proportionality and intersubject and intrasubject variability of pharmacokinetic parameters were examined. Safety assessments included adverse events. All 20 subjects received 50 and 100 mg while 18, 12, and 9 subjects received 150, 200, and 250 mg of lisdexamfetamine dimesylate, respectively. Ten subjects were discontinued during the study for prespecified stopping rules (2 consecutive hourly readings of blood pressure: systolic >160 mm Hg or diastolic >100 mm Hg). Mean maximum observed plasma concentration (C-max) and area under the concentration-time curve from time 0 to infinity (AUC(0-infinity)) increased linearly and dose-dependently for d-amphetamine. Median time to C-max ranged from 4 to 6 hours for d-amphetamine and 1.0 to 1.5 hours for lisdexamfetamine dimesylate. Intersubject and intrasubject variability over doses from 50 to 150 mg was low (<20%) for both C-max and AUC(0-infinity). Adverse events included nausea, dizziness, headache, psychomotor hyperactivity, and dysuria. These findings indicate that the pharmacokinetic parameters of d-amphetamine were dose-proportional and predictable over a wide range of lisdexamfetamine dimesylate doses.
引用
收藏
页码:1001 / 1010
页数:10
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