Pharmacokinetics of Lisdexamfetamine Dimesylate after Targeted Gastrointestinal Release or Oral Administration in Healthy Adults

Ermer, James; Haffey, Mary B.; Döll, W; Martin, Patrick; Sandefer, Erik P.; Dennis, Kerry; Corcoran, Mary; Trespìdi, Laura; Page, Richard C.

doi:10.1124/dmd.111.040691

Cited by 19 publications

(13 citation statements)

References 32 publications

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“…To the best of our knowledge there are no articles related to detection of LDX in oral fluid and the existing articles related to plasma and urine methods for LDX lack information (Biederman et al, 2007;Boellner, Stark, Krishnan, & Zhang, 2010;Ermer, Corcoran, & Martin, 2015;Ermer, Haffey, Richards, Lasseter, Adeyi et al, 2013a;Ermer, Haffey, Richards, Lasseter, Roesch et al, 2013b;Ermer et al, 2011Ermer et al, , 2012Jasinski & Krishnan, 2009;Krishnan, Pennick, & Stark, 2008;Krishnan & Zhang, 2008;Pennick, 2010, 2 | MATERIALS AND METHODS…”

Section: Introductionmentioning

confidence: 99%

Method validation and determination of lisdexamfetamine and amphetamine in oral fluid, plasma and urine by LC–MS/MS

Comiran

Barreto

Meneghini

et al. 2016

Biomedical Chromatography

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Lisdexamfetamine (LDX) is a long-acting prodrug stimulant indicated for the treatment of attention-deficit/hyperactivity disorder and binge-eating disorder symptoms. In vivo hydrolysis of LDX amide bond releases the therapeutically active d-amphetamine (d-AMPH). Since toxicological tests in biological samples can detect AMPH from the use of some legal medications, efficient methods are needed in order to correctly interpret the results. The aim of this study was to develop and validate an LC-MS/MS method for the simultaneous quantification of LDX and its main biotransformation product AMPH in human oral fluid, plasma and urine. Calibration curve range for both analytes was 1-128 ng/mL in oral fluid and plasma and 4-256 ng/mL in urine, being the lowest concentration the limit of quantification. Accuracy of the determined values of the target analytes for the five control levels ranged from 94.8 to 111.7% for oral fluid, from 91.3 to 100.2% for plasma and from 94.8 to 109.8% for urine. Imprecision for the five control levels did not exceeded 12.8% for oral fluid, 16.2% for plasma and 17.1% for urine. The method developed for the three matrices was validated and was also successfully applied to assess real samples, showing for the first time the detection of LDX in oral fluid.

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Section: Introductionmentioning

confidence: 99%

Method validation and determination of lisdexamfetamine and amphetamine in oral fluid, plasma and urine by LC–MS/MS

Comiran

Barreto

Meneghini

et al. 2016

Biomedical Chromatography

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“…In weeks 1–4, one extended visit per week occurs for detailed data collection concerning the safety and efficacy outcomes. Selected timed assessments (as outlined in Table 1) are conducted pre-dose dispensing (trough level, equivalent to LDX steady state) and four hours post dosing for peak levels [31]. In the follow up period 4 weeks after the final dose, an additional extended visit will assess the same safety and efficacy outcomes measured in the dose-escalation period.…”

Section: Methodsmentioning

confidence: 99%

Study protocol: a dose-escalating, phase-2 study of oral lisdexamfetamine in adults with methamphetamine dependence

et al. 2016

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BackgroundThe treatment of methamphetamine dependence is a continuing global health problem. Agonist type pharmacotherapies have been used successfully to treat opioid and nicotine dependence and are being studied for the treatment of methamphetamine dependence. One potential candidate is lisdexamfetamine, a pro-drug for dexamphetamine, which has a longer lasting therapeutic action with a lowered abuse potential. The purpose of this study is to determine the safety of lisdexamfetamine in this population at doses higher than those currently approved for attention deficit hyperactivity disorder or binge eating disorder.Methods/designThis is a phase 2 dose escalation study of lisdexamfetamine for the treatment of methamphetamine dependence. Twenty individuals seeking treatment for methamphetamine dependence will be recruited at two Australian drug and alcohol services. All participants will undergo a single-blinded ascending-descending dose regime of 100 to 250 mg lisdexamfetamine, dispensed daily on site, over an 8-week period. Participants will be offered counselling as standard care. For the primary objectives the outcome variables will be adverse events monitoring, drug tolerability and regimen completion. Secondary outcomes will be changes in methamphetamine use, craving, withdrawal, severity of dependence, risk behaviour and other substance use. Medication acceptability, potential for non-prescription use, adherence and changes in neurocognition will also be measured.DiscussionDetermining the safety of lisdexamfetamine will enable further research to develop pharmacotherapies for the treatment of methamphetamine dependence.Trial registrationAustralian and New Zealand Clinical Trials Registry ACTRN12615000391572 Registered 28th April 2015.

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“…In healthy adult volunteers, a steady-state concentration of dextroamphetamine following administration of lisdexamfetamine 70 mg was achieved by day 5 12. Consistent levels of mean peak plasma concentration (C max ) and area under the curve for dextroamphetamine were recorded when healthy adult volunteers were administered lisdexamfetamine 50 mg using oral capsules and InteliSite™ delivery capsules (Casper Associates, Raleigh, NC, USA) designed to release the drug selectively in selected small intestinal regions 13. Time to reach maximal concentration was delayed by one hour when 70 mg of lisdexamfetamine was administered with food compared with the fasting state in healthy adult volunteers, but there was no change in C max levels 14.…”

Section: Pharmacologic Aspectsmentioning

confidence: 99%

Update on optimal use of lisdexamfetamine in the treatment of ADHD

Madaan¹,

Kolli²,

Bestha³

et al. 2013

NDT

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Lisdexamfetamine (LDX) has been a recent addition to the treatment armamentarium for Attention Deficit Hyperactivity Disorder (ADHD). It is unique among stimulants as it is a prodrug, and has been found to be safe and well-tolerated medication in children older than 6 years, adolescents and adults. It has a smooth onset of action, exerts its action up to 13 hours and may have less rebound symptoms. LDX has proven to be effective in the treatment of ADHD in placebo controlled trials, and improved performance in simulated academic and work environments have been noticed. Both stimulant-naïve and stimulant-exposed patients with ADHD appear to benefit from LDX. It has also shown some promise in improving emotional expression and executive function of patients with ADHD. Adverse effects such as decrease in sleep, loss of appetite and others have been reported with LDX use, just as with other stimulant formulations. Since most such studies exclude subjects with preexisting cardiac morbidity, prescribing precautions should be taken with LDX in such subjects, as with any other stimulant. Study subjects on LDX have been reported to have low scores on drug likability scales, even with intravenous use; as a result, LDX may have somewhat less potential for abuse and diversion. There is a need for future studies comparing other long acting stimulants with LDX in ADHD; in fact clinical trials comparing LDX with OROS (osmotic controlled-release oral delivery system) methylphenidate are currently underway. Furthermore, the utility of this medication in other psychiatric disorders and beyond ADHD is being investigated.

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Pharmacokinetics of Lisdexamfetamine Dimesylate after Targeted Gastrointestinal Release or Oral Administration in Healthy Adults

Cited by 19 publications

References 32 publications

Method validation and determination of lisdexamfetamine and amphetamine in oral fluid, plasma and urine by LC–MS/MS

Method validation and determination of lisdexamfetamine and amphetamine in oral fluid, plasma and urine by LC–MS/MS

Study protocol: a dose-escalating, phase-2 study of oral lisdexamfetamine in adults with methamphetamine dependence

Update on optimal use of lisdexamfetamine in the treatment of ADHD

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