Pharmacokinetics and Pharmacodynamics of Lisdexamfetamine Compared with D-Amphetamine in Healthy Subjects

Dolder, Patrick C.; Strajhar, Petra; Vizeli, Patrick; Hammann, Felix; Odermatt, Alex; Liechti, Matthias E.

doi:10.3389/fphar.2017.00617

Cited by 39 publications

(56 citation statements)

References 50 publications

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“…For 4‐FA, the half‐lives were in 11 of 17 cases in the range of 8–10 hours, for amphetamine this varied much more with half‐lives in the range of 6−12 hours in 12 of 16 cases ( n = 12 in the 100 mg and n = 5 in the 150 mg dose conditions combined). Though it must be considered that amphetamine concentrations were in a much lower range than 4‐FA concentrations (less than 5 ng/mL vs 59–315 ng/mL), the results for amphetamine are in agreement with experiences in previous studies of oral amphetamine application where half‐lives in the range of 6.9−14 hours were found . In the present study, half‐lives of 4‐FA were shorter than those of amphetamine if compared in the same subjects (−16.2%, range − 43.6%−11.7%).…”

Section: Discussionsupporting

confidence: 91%

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Pharmacokinetic properties of 4‐fluoroamphetamine in serum and oral fluid after oral ingestion

Toennes

Schneider

Pogoda

et al. 2019

Drug Testing and Analysis

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Introduction Each year, synthetic drugs occur in high numbers on the illicit drug market. But data on their pharmacology and toxicology are scarce. Therefore, a controlled study was performed to evaluate pharmacokinetic parameters of 4‐fluoroamphetamine (4‐FA) in humans and to compare it with effects. Methods Twelve subjects ingested 100 mg and five subjects also received 150 mg 4‐FA in a bitter lemon drink. Blood and oral fluid samples were taken during the following 12 hours and analyzed for 4‐FA and traces of amphetamine as impurity by liquid chromatography−tandem mass spectrometry (LC–MS/MS). Results For 12 hours after ingestion, the concentration‐time course of 4‐FA was similar to that of amphetamine with maximal concentrations appearing in serum after about 2 hours (in median 195 ng/mL after the 100 mg dose, range 155–316 ng/mL). The elimination half‐life was approximately 8–9 hours and shorter than that of amphetamine but it exhibited a marked variation (5.5–16.8 hours). In oral fluid, 4‐FA could also be detected for 12 hours and concentrations were higher than in serum. During the first 3 hours after ingestion concentrations were higher, most probably due to oral contamination. Serum concentrations in forensic cases were in the range of those observed in the present study suggesting dosages in recreational use in the range of those tested here. Conclusions The pharmacokinetic properties of 4‐FA are similar to that of amphetamine including a marked variation in elimination. However, recreational dosages may already exhibit prominent adverse effects and may even have life‐threatening consequences.

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Section: Discussionsupporting

confidence: 91%

“…the results for amphetamine are in agreement with experiences in previous studies of oral amphetamine application where half-lives in the range of 6.9−14 hours were found. 14,18,19 In the present study, half-…”

Section: Pharmacokinetic Properties Of 4-fa and Amphetamine In Serummentioning

confidence: 77%

Pharmacokinetic properties of 4‐fluoroamphetamine in serum and oral fluid after oral ingestion

Toennes

Schneider

Pogoda

et al. 2019

Drug Testing and Analysis

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“…The washout periods between sessions were at least 7 days. Only the novel LSD and placebo data are presented here because the PK and PD of the MDMA and D‐amphetamine formulations that were used in the study have previously been published and because the sampling time was too short to provide full concentration–time curves for these substances with long half‐lives.…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetics and subjective effects of a novel oral LSD formulation in healthy subjects

Holze

Duthaler

Vizeli

et al. 2019

Brit J Clinical Pharma

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Aims:The aim of the present study was to characterize the pharmacokinetics and exposure-subjective response relationship of a novel oral solution of lysergic acid diethylamide (LSD) that was developed for clinical use in research and patients.Method: LSD (100 μg) was administered in 27 healthy subjects using a placebocontrolled, double-blind, cross-over design. Plasma levels of LSD, nor-LSD, and 2oxo-3-hydroxy-LSD (O-H-LSD) and subjective drug effects were assessed up to 11.5 hours.Results: First-order elimination kinetics were observed for LSD. Geometric mean maximum concentration (C max ) values (range) of 1.7 (1.0-2.9) ng/mL were reached at a t max (range) of 1.7 (1.0-3.4) hours after drug administration. The plasma halflife (t 1/2 ) was 3.6 (2.4-7.3) hours. The AUC ∞ was 13 (7.1-28) ng·h/mL. No differences in these pharmacokinetic parameters were found between male and female subjects. Plasma O-H-LSD but not nor-LSD (< 0.01 ng/mL) concentrations could be quantified in all subjects. Geometric mean O-H-LSD C max values (range) of 0.11 (0.07-0.19)ng/mL were reached at a t max (range) of 5 (3.2-8) hours. The t 1/2 and AUC ∞ values of O-H-LSD were 5.2 (2.6-21) hours and 1.7 (0.85-4.3) ng·h/mL, respectively. The subjective effects of LSD lasted (mean ± SD) for 8.5 ± 2.0 hours (range: 5.3-12.8 h), and peak effects were reached 2.5 ± 0.6 hours (range 1.6-4.3 h) after drug administration. EC 50 values were 1.0 ± 0.5 ng/mL and 1.9 ± 1.0 ng/mL for "good"and "bad" subjective drug effects, respectively. Conclusion:The present study characterized the pharmacokinetics of LSD and its main metabolite O-H-LSD. The subjective effects of LSD were closely associated with changes in plasma concentrations over time.

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“…In a study in healthy adults, systemic exposure to d ‐ amphetamine was around 20 times higher than that of intact lisdexamfetamine . In addition, d ‐ amphetamine or lisdexamfetamine bioavailability in healthy adults does not appear to be significantly affected by food, and the pharmacokinetics of lisdexamfetamine or d ‐ amphetamine has been found to be consistent between men and women …”

Section: Introductionmentioning

confidence: 98%

“…6 In addition, d-amphetamine or lisdexamfetamine bioavailability in healthy adults does not appear to be significantly affected by food, 7 and the pharmacokinetics of lisdexamfetamine or d-amphetamine has been found to be consistent between men and women. 8 Within 6 hours postadministration, lisdexamfetamine was completely eliminated from subjects in a phase 1 study of oral lisdexamfetamine 70 mg/d in healthy adults. Prior pharmacological treatment had no impact on the dose-response efficacy of lisdexamfetamine (30-70 mg/d) in a 4 week, randomized, placebo-controlled, forced-dose titration study in adults with ADHD.…”

Section: Introductionmentioning

confidence: 99%

A phase 1, randomized, double‐blind, placebo‐controlled study to evaluate the safety, tolerability, and pharmacokinetics of single and multiple doses of lisdexamfetamine dimesylate in Japanese and Caucasian healthy adult subjects

Ermer

Martin

Corcoran

et al. 2019

Neuropsychopharm Rep

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Aim To assess safety, tolerability, and pharmacokinetics of lisdexamfetamine dimesylate in Japanese and Caucasian healthy adults. Methods A phase 1, double‐blind, randomized, placebo‐controlled, single‐ and multiple‐dose study in Japanese and Caucasian subjects. Subjects received lisdexamfetamine 20 mg or placebo on Day 1, then lisdexamfetamine 20 mg/d (Days 4‐8), 50 mg/d (Days 9‐13), 70 mg/d (Days 14‐18), or matching placebo. Pharmacokinetic parameters for lisdexamfetamine and d‐amphetamine were estimated by noncompartmental analysis. Results Fifteen Japanese and 19 Caucasian subjects were enrolled and randomized. The lisdexamfetamine and d‐amphetamine plasma concentration‐time curves were similar for both ethnic groups following single and multiple doses. Mean area under the concentration‐time curves for d‐amphetamine were higher (by 11%‐15%) in Japanese than Caucasian subjects following multiple dosing of lisdexamfetamine. Mean bodyweight was 17% lower in Japanese than Caucasian subjects. Weight‐corrected means for oral clearance were similar in both ethnic groups, with no unexpected accumulation of d‐amphetamine. Lisdexamfetamine was generally well tolerated by both ethnic groups, with no serious adverse events reported. The 10/12 Japanese and 11/16 Caucasian subjects who received lisdexamfetamine completed the study; two Japanese and three Caucasian subjects discontinued due to adverse events. Most adverse events were of mild severity. Conclusion Pharmacokinetics were generally similar for Japanese and Caucasian subjects; the minor differences observed were likely due to bodyweight differences in the two ethnic groups. Lisdexamfetamine was generally well tolerated. Adverse events were consistent with the established safety profile of lisdexamfetamine and were similar in both ethnic groups.

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Pharmacokinetics and Pharmacodynamics of Lisdexamfetamine Compared with D-Amphetamine in Healthy Subjects

Cited by 39 publications

References 50 publications

Pharmacokinetic properties of 4‐fluoroamphetamine in serum and oral fluid after oral ingestion

Pharmacokinetic properties of 4‐fluoroamphetamine in serum and oral fluid after oral ingestion

Pharmacokinetics and subjective effects of a novel oral LSD formulation in healthy subjects

A phase 1, randomized, double‐blind, placebo‐controlled study to evaluate the safety, tolerability, and pharmacokinetics of single and multiple doses of lisdexamfetamine dimesylate in Japanese and Caucasian healthy adult subjects

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