PMID- 19820270 OWN - NLM STAT- MEDLINE DCOM- 20091104 LR - 20151119 IS - 1941-9260 (Electronic) IS - 0032-5481 (Linking) VI - 121 IP - 5 DP - 2009 Sep TI - Effects of omeprazole on the pharmacokinetic profiles of lisdexamfetamine dimesylate and extended-release mixed amphetamine salts in adults. PG - 11-9 LID - 10.3810/pgm.2009.09.2048 [doi] AB - 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. FAU - Haffey, Mary B AU - Haffey MB AD - Clinical Pharmacology, Shire Development Inc., Wayne, PA 19087, USA. mhaffey@shire.com FAU - Buckwalter, Mary AU - Buckwalter M FAU - Zhang, Pinggao AU - Zhang P FAU - Homolka, Robert AU - Homolka R FAU - Martin, Patrick AU - Martin P FAU - Lasseter, Kenneth C AU - Lasseter KC FAU - Ermer, James C AU - Ermer JC LA - eng SI - ClinicalTrials.gov/NCT00746733 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - England TA - Postgrad Med JT - Postgraduate medicine JID - 0401147 RN - 0 (Delayed-Action Preparations) RN - 0 (Proton Pump Inhibitors) RN - CK833KGX7E (Amphetamine) RN - KG60484QX9 (Omeprazole) RN - SJT761GEGS (Lisdexamfetamine Dimesylate) RN - TZ47U051FI (Dextroamphetamine) SB - IM MH - Adult MH - Amphetamine/*administration & dosage/*pharmacokinetics MH - Area Under Curve MH - Cross-Over Studies MH - Delayed-Action Preparations MH - Dextroamphetamine/blood/*pharmacokinetics MH - Drug Administration Schedule MH - Female MH - Humans MH - Lisdexamfetamine Dimesylate MH - Male MH - Medication Therapy Management MH - Metabolic Clearance Rate MH - Middle Aged MH - Omeprazole/*administration & dosage MH - Proton Pump Inhibitors/*administration & dosage MH - Young Adult EDAT- 2009/10/13 06:00 MHDA- 2009/11/05 06:00 CRDT- 2009/10/13 06:00 PHST- 2009/10/13 06:00 [entrez] PHST- 2009/10/13 06:00 [pubmed] PHST- 2009/11/05 06:00 [medline] AID - 10.3810/pgm.2009.09.2048 [doi] PST - ppublish SO - Postgrad Med. 2009 Sep;121(5):11-9. doi: 10.3810/pgm.2009.09.2048.