PMID- 23532686
OWN - NLM
STAT- MEDLINE
DCOM- 20131030
LR  - 20151119
IS  - 1179-187X (Electronic)
IS  - 1175-3277 (Linking)
VI  - 13
IP  - 2
DP  - 2013 Apr
TI  - Pharmacokinetics and pharmacodynamics of the antiplatelet combination aspirin 
      (acetylsalicylic acid) plus extended-release dipyridamole are not altered by 
      coadministration with the potent CYP2C19 inhibitor omeprazole.
PG  - 113-20
LID - 10.1007/s40256-013-0018-3 [doi]
AB  - BACKGROUND: The fixed-dose combination of aspirin (acetylsalicylic acid) 25 mg 
      plus extended-release dipyridamole 200 mg (ASA+ER-DP) is used for long-term 
      secondary stroke prevention in patients who have experienced non-cardioembolic 
      stroke or transient ischemic attack. Although the theoretical risk is low that 
      the antiplatelet activity of ASA+ER-DP will be affected by concomitant use of a 
      proton pump inhibitor (PPI), no formal drug-drug interaction studies have been 
      conducted. OBJECTIVE: This study aimed to determine whether the PPI omeprazole 
      influences the pharmacokinetic (PK) and pharmacodynamic (PD) behavior of 
      ASA+ER-DP. STUDY DESIGN AND SETTING: This was a randomized, open-label, 
      multiple-dose, crossover, drug-drug interaction study carried out in a clinical 
      trial unit. PARTICIPANTS: Sixty healthy male and female volunteers aged 18-50 
      years were included in the study. INTERVENTION: Participants were randomized to 
      one of two treatment sequences (ABCD or CDAB), each comprising four 7-day 
      treatments with a washout of >/=14 days between the second and third treatments. 
      Treatment A=ASA+ER-DP 25 mg/200 mg (Aggrenox(R)) twice daily (BID) alone; 
      B=ASA+ER-DP 25 mg/200 mg BID+omeprazole (Prilosec(R)) 80 mg once daily (QD) 
      following ASA+ER-DP alone for 7 days; C=omeprazole 80 mg QD alone; D=omeprazole 
      80 mg QD+ASA+ER-DP 25 mg/200 mg BID following omeprazole alone for 7 days. MAIN 
      OUTCOME MEASURES: The main outcome measures were systemic PK exposure to ER-DP 
      and ASA inhibition of arachidonic acid-induced platelet aggregation. RESULTS: 
      Systemic exposure to ER-DP was similar with and without omeprazole, based on 
      steady-state area under the concentration-time curve (AUC) from 0 to 12 h 
      (AUC0-12,ss, ng.h/mL) and maximum plasma concentration (Cmax,ss, ng/mL). For the 
      treatment comparison D versus A, the percent mean ratios were 96.38 (90% 
      confidence interval [CI] 90.96-102.13) for AUC0-12,ss and 92.03 (86.95-97.40) for 
      Cmax,ss. The ER-DP concentration versus time profiles were nearly superimposable. 
      There was no effect on the PDs of the ASA component: the extent of ASA inhibition 
      of arachidonic acid-induced platelet aggregation was almost identical with and 
      without omeprazole, with a percent mean ratio for treatment D versus A = 99.02 
      (90 % CI 98.32-99.72) at 4 h after last dose. All treatments were well tolerated. 
      CONCLUSION: The PK and PD behavior of ASA + ER-DP was not altered by concurrent 
      administration of omeprazole.
FAU - Offman, Elliot
AU  - Offman E
AD  - Clinical Pharmacology Sciences, Celerion, 100 Boulevard Alexis-Nihon, Bureau 
      (Suite) 360, Montreal, QC, H4M 2N8, Canada. elliot.offman@celerion.com
FAU - Schobelock, Michael J
AU  - Schobelock MJ
FAU - Brickl, Rolf
AU  - Brickl R
FAU - VanderMaelen, Cam P
AU  - VanderMaelen CP
FAU - Ehrlich, Jerome
AU  - Ehrlich J
FAU - Eisert, Wolfgang
AU  - Eisert W
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - New Zealand
TA  - Am J Cardiovasc Drugs
JT  - American journal of cardiovascular drugs : drugs, devices, and other 
      interventions
JID - 100967755
RN  - 0 (Aspirin, Dipyridamole Drug Combination)
RN  - 0 (Drug Combinations)
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - 0 (Proton Pump Inhibitors)
RN  - 64ALC7F90C (Dipyridamole)
RN  - KG60484QX9 (Omeprazole)
RN  - R16CO5Y76E (Aspirin)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aspirin/administration & dosage/adverse effects/*pharmacokinetics
MH  - Aspirin, Dipyridamole Drug Combination
MH  - Cross-Over Studies
MH  - Dipyridamole/administration & dosage/adverse effects/*pharmacokinetics
MH  - Drug Combinations
MH  - Drug Interactions
MH  - Drug Therapy, Combination
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Omeprazole/administration & dosage/adverse effects/*pharmacokinetics
MH  - Platelet Aggregation/*drug effects
MH  - Platelet Aggregation Inhibitors/administration & dosage/adverse 
      effects/*pharmacokinetics
MH  - Proton Pump Inhibitors/administration & dosage/adverse effects/*pharmacokinetics
MH  - Young Adult
EDAT- 2013/03/28 06:00
MHDA- 2013/10/31 06:00
CRDT- 2013/03/28 06:00
PHST- 2013/03/28 06:00 [entrez]
PHST- 2013/03/28 06:00 [pubmed]
PHST- 2013/10/31 06:00 [medline]
AID - 10.1007/s40256-013-0018-3 [doi]
PST - ppublish
SO  - Am J Cardiovasc Drugs. 2013 Apr;13(2):113-20. doi: 10.1007/s40256-013-0018-3.