Research article summary (published 30 Aug 2009):

Effects of omeprazole on the pharmacokinetic profiles of lisdexamfetamine dimesylate and extended-release mixed amphetamine salts in adults.

Full Abstract

OBJECTIVE: To evaluate the pharmacokinetics of lisdexamfetamine dimesylate (LDX), a long-acting prodrug stimulant, and mixed amphetamine salts extended-release (MAS XR), alone or with omeprazole, a proton pump inhibitor (PPI). METHODS: This open-label, randomized, 4-period crossover study enrolled healthy adults (18-45 years). Subjects alternately received single doses of LDX 50 mg and MAS XR 20 mg at 4-day intervals. Following washout, subjects received omeprazole (40 mg/day x 14 days), with alternate single doses of LDX 50 mg or MAS XR 20 mg added on days 7 and 11. Blood samples were collected predose and 0 to 96 hours postdose for pharmacokinetic analysis. Safety assessments included adverse events (AEs). RESULTS: Overall, 24 subjects were randomized; 21 completed the study. For LDX monotherapy, d-amphetamine mean (SD) exposure was 45.0 (13.97) ng/mL and 713.0 (134.75) ng . h/mL; when coadministered with omeprazole it was 46.3 (9.71) ng/mL and 761.6 (191.13) ng . h/mL, for Cmax and AUCinf, respectively. The median Tmax was 3 hours with and without omeprazole. For MAS XR monotherapy, total amphetamine mean (SD) exposure was 36.6 (9.19) ng/mL and 640.8 (95.66) ng . h/mL; when coadministered with omeprazole it was 38.1 (7.35) ng/mL and 643.9 (143.16) ng . h/mL, for Cmax and AUCinf, respectively. The median Tmax was 5 hours and 2.75 hours without and with omeprazole, respectively; 57.1% to 61.9% of subjects receiving MAS XR and 25% receiving LDX showed an earlier (>or= 1 hour) Tmax with omeprazole. Both medications had AEs consistent with amphetamine use. CONCLUSIONS: Total exposure was unaffected by omeprazole for both compounds. However, approximately 50% of subjects receiving MAS XR showed an earlier Tmax while on omeprazole, indicating unpredictable release of active drug by the second bead of MAS XR, most likely related to reduced stomach acid while on a PPI compromising the pulsed delivery of MAS XR. No clear trend was observed for LDX.

Author information

Author/s: Haffey, Mary B (MB); Buckwalter, Mary (M); Zhang, Pinggao (P); Homolka, Robert (R); Martin, Patrick (P); Lasseter, Kenneth C (KC); Ermer, James C (JC);

Affiliation: Clinical Pharmacology, Shire Development Inc., Wayne, PA 19087, USA. mhaffey(-atsign-)shire.com

Journal and publication information

Publication Type: Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

Journal: Postgraduate medicine (Postgrad Med), published in United States. (Language: eng)

Reference: 2009-Sep; vol 121 (issue 5) : pp 11-9

Dates: Created 2009/10/12; Completed 2009/11/04;

PMID: 19820270, status: MEDLINE (last retrieval date: 11/4/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adult Amphetamine - administration & dosage; pharmacokinetics Area Under Curve Cross-Over Studies Delayed-Action Preparations Dextroamphetamine - blood; pharmacokinetics Drug Administration Schedule Female

Humans Male Medication Therapy Management Metabolic Clearance Rate Middle Aged Omeprazole - administration & dosage Proton Pump Inhibitors - administration & dosage Young Adult

Associated Chemicals: Delayed-Action Preparations (0) ; Proton Pump Inhibitors (0) ; lisdexamfetamine dimesylate (0) ; Amphetamine (300-62-9) ; Dextroamphetamine (51-64-9) ; Omeprazole (73590-58-6)

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