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

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.

journal_name

Postgrad Med

journal_title

Postgraduate medicine

authors

Haffey MB,Buckwalter M,Zhang P,Homolka R,Martin P,Lasseter KC,Ermer JC

doi

10.3810/pgm.2009.09.2048

subject

Has Abstract

pub_date

2009-09-01 00:00:00

pages

11-9

issue

eissn

0032-5481

issn

1941-9260

journal_volume

121

pub_type

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