**Author details**

without any risk and to limit their prescription to the validated indications, to the recommended posology, during a well-determined duration, especially to the fragile elderly sub-

The PPI use may increase the risk of medicinal interactions (by modifying the absorption of medicine by acting on the gastric pH or by competition on the cytochrome P450 (CYP)) being able to make tilt the balance profit/risk negatively, at the elderly person. Indeed, by increasing the gastric pH, the PPI decreases the dissolution and the solubilization of some administered medicines per bone, such as antifungals (for example, the itraconazole [45]) or the immunosuppressors (such as the mycophenolate mofetil [46]). On the contrary, they can increase the reduction of some medicines such as the saquinavir [47]. On the other hand, the taking of a PPI could theoretically improve the bioavailability of medicines for which an important part of the ingested dose is normally hydrolyzed in acid area (such as penicillin) [48]. Finally, it was demonstrated that the omeprazole increased the bioavailability of the digoxine [49] and the nifedipine [50] by inhibiting at the intestinal level of the isoenzyme 3A4 of the CYP450

On the other hand, all the PPIs, except the rabeprazole, are mainly metabolized by isoenzymes 2C19 and 3A4 of the CYP, [51]. At the same time, the PPI inhibit these enzymes. The omeprazole is also a moderate inductor of the CYP 1A2 [52]. Thus, pharmacokinetics interaction risk exists with medicines that are major substrata of these isoforms. The particular case of the interaction between the IPP and the clopidogrel, a platelet antiaggregant in which the efficiency depends on its bioactivation by the CYP 2C19, was widely studied, without formal proof of its clinical impact. The clopidogrel belongs to the class of thienopyridines. It is a prodrug, absorbed by the intestine and then transformed into an active metabolite by the liver via two successive reactions of oxidation by cytochromes P450, and more exact isoforms CYP2C19, CYP3A4/5, CYP2C9, and CYP2B6. By inhibiting the CYP 2C19, the PPI (except for a very weak action for the pantoprazole) decreases the clopidogrel activation and thus its efficiency, hence exposing the patients to ischemic accidents. Numerous retrospective studies confirmed this interaction [53]. According to the FDA's to the healthcare professionals of November 17th, 2009, the association of the omeprazole with the clopidogrel is not advisable. The FDA, presented the pantoprazole as a possible alternative in case of necessary association of an IPP with clopidogrel, because of its slightest inhibitive potential on the CYP 2C19 [54]. As far as the inhibition of the CYP 2C19 by the PPI is reversible and considering the short half-life of the PPI, some authors suggested minimizing the clinical consequences of this interaction by prescribing the PPI in the morning and the clopidogrel in the evening with an interval of 12 hours by separating both the takings [55]. However, the published randomized forward-looking studies did not find this interaction and confirmed the beneficial effects of the PPI on the digestive bleedings [31, 56, 57, 58]. In 2012, these data allowed Afssaps (become ANSM: National agency of Safety of the Medicine) to remove, the PPI-clopidogrel interaction

However, the ANSM has issued a reserve in its recommendations of 2012 advising to avoid the clopidogrel-omeprazole and clopidogrel-esomeprazole associations [60]. In our series, two patients were treated with the clopidogrel in association with the PPI and they did not receive any information concerning the possibility of a medicinal interaction. Though

ject treated by a lot of drugs.

142 Esophageal Abnormalities

and the glycoprotein P.

from the thesaurus of the medicinal interactions [59].

Mona Boudabous\*, Héla Gdoura, Leila Mnif, Lassad Chtourou, Amal Grati, Ali Amouri and Nabil Tahri

\*Address all correspondence to: boudabousmona@yahoo.fr

Gastroenterology Department, Hedi Chaker Hospital, Sfax, Tunisia
