Effects of lisdexamfetamine on plasma steroid concentrations compared with d-amphetamine in healthy subjects: A randomized, double-blind, placebo-controlled study. Issue 186 (February 2019)

• Record Type: Journal Article
• Authors: Strajhar, Petra; Vizeli, Patrick; Patt, Melanie; Dolder, Patrick C.; Kratschmar, Denise V.; Liechti, Matthias E.; Odermatt, Alex
• Is Part Of: Journal of steroid biochemistry and molecular biology. Issue 186(2019)
• Page Start: 212
• Page End: 225
• Publication Date: 2019-02
• Subjects: Amphetamine -- Lisdexamfetamine -- Psychostimulant -- Glucocorticoid -- Attention-deficit/hyperactivity disorder; Steroid hormones -- Periodicals; Biochemistry -- Periodicals; Hormones -- Periodicals; Molecular Biology -- Periodicals; Hormones stéroïdes -- Périodiques; Steroid hormones; Periodicals; 572.579
• DOI: 10.1016/j.jsbmb.2018.10.016
• Languages: English
• ISSNs: 0960-0760

Abstract

Graphical abstract: Highlights: Effects of lisdexamfetamine andd -amphetamin on circulating steroids was studied in healthy subjects. Maximal concentrations and total amphetamine exposure were similar for both formulations. Both similarly increased circulating ACTH, glucocorticoids and adrenal androgens. Lisdexamfetamine showed a later onset of steroid increase but comparable maximal levels and AUC. Abstract: The noveld -amphetamine prodrug lisdexamfetamine is applied to treat attention-deficit/hyperactivity disorder (ADHD).d -Amphetamine releases dopamine and norepinephrine and stimulates the hypothalamic-pituitary-adrenal (HPA) axis, which may contribute to its reinforcing effects and risk of abuse. However, no data is currently available on the effects of lisdexamfetamine on circulating steroids. This randomized, double-blind, placebo-controlled, cross-over study evaluated the effects of equimolar doses ofd -amphetamine (40 mg) and lisdexamfetamine (100 mg) and placebo on circulating steroids in 24 healthy subjects. Plasma steroid andd -amphetamine levels were determined up to 24 h. Delayed increase and peak levels of plasmad -amphetamine concentrations were observed following lisdexamfetamine treatment compared withd -amphetamine administration, however the maximal concentrations and total exposure (area under the curve [AUC]) were similar. Lisdexamfetamine andd -amphetamine significantly enhanced plasma levels of adrenocorticotropic hormone, glucocorticoids (cortisol, cortisone, corticosterone, 11-dehydrocorticosterone, and 11-deoxycortisol), androgens (dehydroepiandrosterone, dehydroepiandrosterone sulfate, and Δ4-androstene-3, 17-dione [androstenedione]), and progesterone (only in men) compared with placebo. Steroid concentration-time curves were shifted to later time points due to a non-significantly later onset following lisdexamfetamine administration than afterd -amphetamine, however maximal plasma steroid concentrations and AUCs did not differ between the active treatments. None of the active treatments altered plasma levels of the mineralocorticoids aldosterone and 11-deoxycorticosterone or the androgen testosterone compared with placebo. The effects of the amphetamines on glucocorticoid production were similar to those that were previously reported for methylphenidate (60 mg) but weaker than those for the serotonin releaser 3, 4-methylenedioxymethamphetamine (MDMA; 125 mg) or direct serotonin receptor agonist lysergic acid diethylamide (LSD; 0.2 mg). Lisdexamfetamine produced comparable HPA axis activation and had similar pharmacokinetics thand -amphetamine, except for a delayed time of onset. Thus, serotonin (MDMA, LSD) may more effectively stimulate the HPA axis than dopamine and norepinephrine (D-amphetamine).