Clinical efficacy of proton pump inhibitor therapy in neurologically impaired children with gastroesophageal reflux: prospective study. Visual disorders associated with omeprazole and their relation to CYP2C19 polymorphism. Rx drugs

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ikp-stuttgart.de

Proton pump inhibitors are a class of drugs which are widely prescribed for acid-related diseases. They are primarily metabolized by CYP2C19 and CYP3A4. It is unknown so far whether proton pump inhibitors are also substrates of the ATP-dependent efflux transporter P-glycoprotein. Moreover, it is not established whether proton pump inhibitors are also inhibitors of P-glycoprotein function. The aim of our study was therefore to characterize omeprazole, lansoprazole and pantoprazole as P-glycoprotein substrates and inhibitors. Polarized transport of these compounds was assessed in P-glycoprotein-expressing Caco-2 and L-MDR1 cells. Inhibition of P-glycoprotein-mediated transport was determined using the cyclosporine analogue PSC-833 (valspodar) as P-glycoprotein inhibitor. Inhibition of efflux transport by omeprazole, lansoprazole and pantoprazole was assessed using digoxin as P-glycoprotein substrate. At concentrations of 5 microM, basal-to-apical transport of omeprazole, lansoprazole and pantoprazole was greater than apical-to-basal transport in Caco-2 and L-MDRI cells. Addition of PSC-833 (1 microM) showed a clear effect only for lansoprazole, suggesting that other transporters contribute to omeprazole and pantoprazole cellular translocation. Furthermore, all of the tested compounds inhibited digoxin transport with IC50 values of 17.7, 17.9 and 62.8 microM for omeprazole, pantoprazole and lansoprazole, respectively. In summary, our data provide evidence that proton pump inhibitors are substrates and inhibitors of P-glycoprotein. These findings might explain some of the drug interactions with proton pump inhibitors observed in vivo.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11770010&dopt=Abstract

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Hong Kong Med J. 2001 Dec;7(4):356-9.
Clinical efficacy of proton pump inhibitor therapy in neurologically impaired children with gastroesophageal reflux: prospective study.

Cheung KM, Tse PW, Ko CH, Chan YC, Leung CY, Chan KH.

Department of Paediatrics, Caritas Medical Centre, 111 Wing Hong Street, Shamshuipo, Kowloon, Hong Kong.

OBJECTIVE: To study the effects of proton pump inhibitors in reducing vomiting, gastrointestinal bleeding, and chest infections in institutionalised neurologically impaired children with gastroesophageal reflux. DESIGN: Prospective study. SETTING: A regional hospital, Hong Kong. PATIENTS: Neurologically impaired children with refractory gastroesophageal reflux. MAIN OUTCOME MEASURES: Episodes of vomiting, gastrointestinal bleeding, and pneumonia in the baseline and proton pump inhibitor treatment periods. RESULTS: Nine children received proton pump inhibitor therapy for a median duration of 81 days. Mean reflux index was 9.3% (standard deviation, 5%). Dosage of omeprazole used was 1.0-2.3 mg/kg/d. Vomiting was reduced significantly with proton pump inhibitor treatment (median vomiting index [baseline]=0.4, median vomiting index [proton pump inhibitors]=0.2; P<0.05). No significant decrease in gastrointestinal bleeding or chest infection was observed. CONCLUSION: Proton pump inhibitors significantly reduced vomiting episodes in neurologically impaired children with gastroesophageal reflux.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11773669&dopt=Abstract

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Pharmacogenetics. 2002 Jan;12(1):73-5.
Visual disorders associated with omeprazole and their relation to CYP2C19 polymorphism.

Lutz M, Schwab M, Griese EU, Marx C, Muller-Oerlinghausen B, Schonhofer PS, Meisner C, Gleiter CH, Eichelbaum M, Morike K.

Division of Clinical Pharmacology, University Hospital Tubingen, Germany.

Risk factors for patients developing visual disturbances in association with proton pump inhibitors are unknown. As omeprazole is substantially metabolized by polymorphic CYP2C19, we retrospectively identified and genotyped patients who experienced this adverse reaction. Among 29 patients, we found two poor metabolizers (PMs) of CYP2C19. The PM genotype does not appear to be a risk factor for omeprazole-associated visual disorders.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11773867&dopt=Abstract

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