Lack of in vitro interactions using human liver microsomes between rabeprazole and anticancer drugs.
The potential interactions between rabeprazole, a widely used proton pump inhibitor, and anticancer drugs (5-fluorouracil, docetaxel, cyclophosphamide, gemcitabine, methotrexate, doxorubicin, etoposide) or drugs commonly present in the therapy of oncological patients (fluoxetine and ondansetron), were studied using in vitro human liver microsomes. The interactions between rabeprazole and the anticancer drugs were evaluated by measuring their concentrations in test and control incubations with HPLC-DAD-UV methods. To achieve this aim, nine HPLC-DAD-UV methods were developed using different stationary and mobile phases. The methods were then validated for the following parameters: selectivity, linearity, precision, and accuracy. As expected rabeprazole did not significantly inhibit the metabolism of the evaluated drugs in human liver microsomal preparations at the selected concentrations. These results shows that rabeprazole probably could be devoid of pharmacokinetic interactions with common drugs used during chemotherapy.
Tamaro
Ilaria
I
Dipartimento di Scienze Chimiche, Alimentari, Farmaceutiche e Farmacologiche, Università degli Studi del Piemonte Orientale A. Avogadro and Drug and Food Biotecnology Center, Novara, Italy.
Genazzani
Armando
A
Canonico
Pierluigi
P
Grosa
Giorgio
G
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D000932:Antiemetics / Q000494:pharmacology; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003520:Cyclophosphamide / Q000494:pharmacology; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D000077143:Docetaxel; D004317:Doxorubicin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005047:Etoposide / Q000494:pharmacology; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008297:Male; D008727:Methotrexate / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects*; D017294:Ondansetron / Q000494:pharmacology; D064750:Rabeprazole; D012015:Reference Standards; D043823:Taxoids / Q000494:pharmacology; D000093542:Gemcitabine
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000903:Antibiotics, Antineoplastic; D018687:Antidepressive Agents, Second-Generation; D000932:Antiemetics; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D043823:Taxoids; D005473:Fluoxetine; D003841:Deoxycytidine; D000077143:Docetaxel; D064750:Rabeprazole; D017294:Ondansetron; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate; D000093542:Gemcitabine