Clopidogrel and proton pump inhibitor (PPI) interaction: separate intake and a non-omeprazole PPI the solution?
BACKGROUND
Dual therapy with aspirin and clopidogrel increases the risk of gastrointestinal bleeding. Therefore, co-therapy with a proton pump inhibitor (PPI) is recommended by most guidelines. However, there are warnings against combining PPIs with clopidogrel because of their interactions with cytochrome P450 isoenzyme 2C19 (CYP2C19).


METHODS
The effects of the combined or separate intake of 20 mg of omeprazole and 75 mg of clopidogrel on the clopidogrel-induced inhibition of platelet aggregation were measured in four healthy subjects whose CYP2C19 exon sequences were determined. The effects of co-therapy with 10 mg of rabeprazole were also examined.


RESULTS
Two subjects showed the wild-type CYP2C19 sequence. The concurrent intake of omeprazole had no effect on clopidogrel-induced platelet inhibition in these subjects. Two subjects were heterozygous for the *2 allele, with predicted reduced CYP2C19 activity. One of them was a clopidogrel non-responder. In the second heterozygous subject, omeprazole co-therapy reduced the clopidogrel anti-platelet effect when taken simultaneously or separately. However, the simultaneous intake of rabeprazole did not reduce the clopidogrel effect.


CONCLUSIONS
The clopidogrel-PPI interaction does not seem to be a PPI class effect. Rabeprazole did not affect the clopidogrel effect in a subject with a clear omeprazole-clopidogrel interaction. The separate intake of PPI and clopidogrel may not be sufficient to prevent their interaction.
Kenngott
S
S
Internistische Klinik Dr. Müller, Am Isarkanal 36, 81379 Munich, Germany.
Olze
R
R
Kollmer
M
M
Bottheim
H
H
Laner
A
A
Holinski-Feder
E
E
Gross
M
M
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000494:pharmacology; D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000502:physiology; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D064750:Rabeprazole; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D064750:Rabeprazole; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole; D013988:Ticlopidine