Aciphex
Cost-minimization analysis of treatment of gastroesophageal reflux disease. Implications of varying holding time on conclusions.

Kivioja A, Linnosmaa I, Vehvilainen A, Vohlonen I.

Department of Social Pharmacy, Center for Pharmaceutical Policy and Economics, University of Kuopio, P.O. Box 1627, FIN-70211, Kuopio, Finland. akseli.kivioja uku.fi

Gastroesophageal reflux disease (GERD), is a common disorder. The most effective medical treatment for GERD is a proton pump inhibitor (PPI). The aim of this study was to specify the most inexpensive PPI therapy for GERD, and to examine the implications of varying outcome measure, holding time, on the conclusions about the cost-effectiveness of the treatments. Proton pump inhibitors that have holding time of intragastric pH>4 for at least 11h in 24h period (esomeprazole, lansoprazole, omeprazole and rabeprazole), were included. In this cost-minimization analysis (CMA), data on holding times were gathered from scientific publications listed in MEDLINE, prices of proton pump inhibitors from the Finnish database of drug prices and the treatment dosages were taken from the official guide of drug therapies in Finland. A decision tree was applied and the probabilities utilized were acquired from three expert physicians. The cost-minimization analysis was performed in three settings. At first, drugs that had a holding time (pH>4) of 11h or more were included. Secondly, drugs that had a holding time of 12h or more were included, and thirdly, a holding time of 13h or more was required. In the first analysis, the least expensive PPI treatment was lansoprazole (average cost of 138.89 per patient). In the second analysis, least expensive treatment was rabeprazole (193.81 per patient), and in the third, rabeprazole again (193.81 per patient). Esomeprazole and omeprazole were not among two of the least expensive alternatives in any of the settings. Which proton pump therapy turns out to be the least expensive for GERD, depends on the length of the holding time desired. Varying the holding time of the drug had a profound effect on the conclusions about the cost-effectiveness of the alternative treatments.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14757488&dopt=Abstract rabeprazole Aciphex



Aciphex
Voltammetric behaviour of rabeprazole at a glassy carbon electrode and its determination in tablet dosage form.

Radi A, Abd El-Ghany N, Wahdan T.

Department of Chemistry, Faculty of Science, Mansoura University, Dumyat 34517, Egypt. abdradi yahoo.com

The oxidative behaviour of rabeprazole was studied at a glassy carbon electrode in Britton-Robinson (BR) buffer solutions using cyclic, linear sweep and differential-pulse voltammetry. The oxidation process was shown to be irreversible over the pH range (6.0-11.0) and was diffusion-adsorption controlled. An analytical method was developed for the determination of rabeprazole in BR buffer solution at pH 8.0 as supporting electrolyte. The anodic peak current varied linearly with rabeprazole concentration in the range 1.0 x 10(-6) to 2.0 x 10(-5) M of rabeprazole with a limit of detection of 4.0 x 10(-7) M. Validation parameters, such as sensitivity, accuracy, precision and recovery, were evaluated. The proposed method was applied to the determination of rabeprazole in the tablet dosage form. The results were compared with those obtained by a published high-performance liquid chromatographic method. No difference was found statistically.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15231426&dopt=Abstract rabeprazole Aciphex



Aciphex
Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities.

Li XQ, Andersson TB, Ahlstrom M, Weidolf L.

DMPK and Bioanalytical Chemistry, AstraZeneca R and D Molndal, S-431 83 Molndal, Sweden.

The human clearance of proton pump inhibitors (PPIs) of the substituted benzimidazole class is conducted primarily by the hepatic cytochrome P450 (P450) system. To compare the potency and specificity of the currently used PPIs (i.e., omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole) as inhibitors of four cytochrome P450 enzymes (CYP2C9, 2C19, 2D6, and 3A4), we performed in vitro studies using human liver microsomal preparations and recombinant CYP2C19. Sample analysis was done using selected reaction monitoring liquid chromatography/tandem mass spectometry. With several systems for CYP2C19 activity (two marker reactions, S-mephenytoin 4'-hydroxylation and R-omeprazole 5-hydroxylation, tested in either human liver microsomes or recombinant CYP2C19), the five PPIs showed competitive inhibition of CYP2C19 activity with K(i) of 0.4 to 1.5 microM for lansoprazole, 2 to 6 microM for omeprazole, approximately 8 microM for esomeprazole, 14 to 69 microM for pantoprazole, and 17 to 21 microM for rabeprazole. Pantoprazole was a competitive inhibitor of both CYP2C9-catalyzed diclofenac 4'-hydroxylation and CYP3A4-catalyzed midazolam 1'-hydroxylation (K(i) of 6 and 22 microM, respectively), which were at least 2 times more potent than the other PPIs. All PPIs were poor inhibitors of CYP2D6-mediated bufuralol 1'-hydroxylation with IC(50) > 200 microM. The inhibitory potency of a nonenzymatically formed product of rabeprazole, rabeprazole thioether, was also investigated and showed potent, competitive inhibition with K(i) values of 6 microM for CYP2C9, 2 to 8 microM for CYP2C19, 12 microM for CYP2D6, and 15 microM for CYP3A4. The inhibitory potency of R-omeprazole on the four studied P450 enzymes was also studied and showed higher inhibitory potency than its S-isomer on CYP2C9 and 2C19 activities. Our data suggest that, although the inhibitory profiles of the five studied PPIs were similar, lansoprazole and pantoprazole are the most potent in vitro inhibitors of CYP2C19 and CYP2C9, respectively. Esomeprazole showed less inhibitory potency compared with omeprazole and its R-enantiomer. The inhibitory potency of rabeprazole was relatively lower than the other PPIs, but its thioether analog showed potent inhibition on the P450 enzymes investigated, which may be clinically significant.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15258107&dopt=Abstract rabeprazole Aciphex