Drugs online research references









Ann Otol Rhinol Laryngol. 2002 Oct;111(10):933-8.
Prospective study on the incidence of chronic ear complaints related to gastroesophageal reflux and on the outcome of antireflux therapy.

Poelmans J, Tack J, Feenstra L.

Department of Otorhinolaryngology-Head and Neck Surgery, University Hospitals Leuven, Belgium.

Over a 2-year period (1997 to 1999), 5 consecutive adult patients with chronic refractory secretory otitis media (CSOM) and 16 with a chronic refractory feeling of pressure in the ear(s) (CRFP) thought to be related to concomitant eustachian tube dysfunction were prospectively studied for coexisting gastroesophageal reflux (GER). All patients underwent an extensive standardized otorhinolaryngological examination, ambulatory 24-hour dual-probe esophageal pH monitoring with a distal pH probe 5 cm and a proximal probe 20 cm above the lower esophageal sphincter, and upper gastrointestinal endoscopy. Most of them also underwent esophageal manometry. All patients with CSOM and 12 of the 16 patients with CRFP had evidence of GER. Only 5 patients experienced heartburn or regurgitation. All patients responded very well to antireflux therapy with omeprazole 20 mg twice per day (40 mg twice per day in 2 patients) accompanied by conservative antireflux measures, ie, complete cessation of their middle ear complaints. This study demonstrates the role of GER in the pathogenesis of refractory CSOM and CRFP and the effectiveness of sustained antireflux therapy.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12389864&dopt=Abstract

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J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Nov 25;780(2):459-65.
Phenotype of CYP2C19 and CYP3A4 by determination of omeprazole and its two main metabolites in plasma using liquid chromatography with liquid-liquid extraction.

Gonzalez HM, Romero EM, Chavez Tde J, Peregrina AA, Quezada V, Hoyo-Vadillo C.

Laboratories de Investigacion y Desarrollo Farmaceutico, Departamento de Farmacobiologia, Universidad de Guadalajara, 44840 Guadalajara, Jal, Mexico.

We present a new simple and reliable HPLC method for measuring omeprazole and its two main metabolites in plasma. This can be used for studying CYP2C19 and CYP3A4 genetic polymorphisms using omeprazole as the probe drug. Omeprazole, hydroxyomeprazole and omeprazole sulfone were extracted from plasma samples with phosphate buffer and dichloromethane-ether (95:5). HPLC separation was achieved using an Ultrasphere ODS C(18) (Beckman) column. The mobile phase was acetonitrile-phosphate buffer (24:76, pH 8), containing nonylamine at 0.015%. Retention times were 9.5 min for omeprazole, 3.25 min for hydroxyomeprazole, 7.4 min for omeprazole sulfone and 6.27 min for internal standard (phenacetine). Detection (UV at 302 nm) of analytes was linear in the range from 96 to 864 ng/ml. This is useful for calculating metabolic index for CYP2C19 and CYP3A4 in adults and children. This method is stable, reproducible, improves resolution and has practical advantages such as low cost. Copyright 2002 Elsevier Science B.V.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12401374&dopt=Abstract

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Gastroenterology. 2002 Nov;123(5):1588-97.
Restoration of acid secretion following treatment with proton pump inhibitors.

Shin JM, Sachs G.

Department of Physiology and Medicine, University of California at Los Angeles, and VA Greater Los Angeles Healthcare System, Los Angeles, California, USA.

BACKGROUND & AIMS: Proton pump inhibitors (PPIs) are covalent inhibitors of the gastric H+,K+-adenosine triphosphatase (ATPase) forming disulfide bonds. Recovery of acid secretion after PPI inhibition may be due to de novo synthesis of pump protein and/or disulfide reduction and reactivation of inhibited pump. The half-time of recovery of acid secretion in rats following omeprazole treatment is approximately 15 hours, whereas pump protein half-life is 54 hours. In humans, the half-life of the inhibitory effect on acid secretion is approximately 28 hours for omeprazole and approximately 46 hours for pantoprazole. Whereas all PPIs bind to cysteine 813, pantoprazole additionally binds to cysteine 822, deeper in the membrane domain of TM6. Their different durations of action may reflect different rates of pump reactivation due to differing accessibility of the disulfides to glutathione. METHODS: Rats were stimulated and treated with 30 mg/kg of each PPI. Gastric ATPase was prepared and reversal of inhibition of the H+,K+-ATPase was measured as the time-dependent restoration of activity by incubation with dithiothreitol or glutathione. RESULTS: One hundred percent reactivation of ATPase following inhibition in vivo by omeprazole or its enantiomers was seen with dithiothreitol and 89% with glutathione. Similar data were found for lansoprazole or rabeprazole. No reactivation by either reducing agent was seen following inhibition by pantoprazole. CONCLUSIONS: Recovery of acid secretion following inhibition by all PPIs, other than pantoprazole, may depend on both protein turnover and reversal of the inhibitory disulfide bond. In contrast, recovery of acid secretion after pantoprazole may depend entirely on new protein synthesis.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12404233&dopt=Abstract

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