Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new lansoprazole research articles will be listed here shortly after becoming available to us.
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Medical research on lansoprazole
Drug Saf. 2008; 31(7): 627-36
Estborn L, Joelson S
BACKGROUND: A potential causal association between an increase in gastric pH and a risk of community-acquired respiratory tract infection (RTI), specifically pneumonia, has been debated in relation to the use of potent gastric acid-suppressive medication. OBJECTIVE: To investigate the occurrence of community-acquired RTI, including pneumonia, in patients receiving esomeprazole versus placebo and other acid-suppressive agents in randomized clinical trials. METHODS: The AstraZeneca ARIADNE safety database was searched for comparative, controlled phase II-IV randomized, blinded clinical studies with esomeprazole and standard reporting of all adverse events (AEs). Pooled AE data were presented according to treatment comparison (esomeprazole versus placebo, esomeprazole 40 mg versus 20 mg daily, esomeprazole versus omeprazole, lansoprazole and/or ranitidine, respectively). Frequency and relative risk (RR), with 99% confidence interval (CI) and adjustment for time on treatment, were calculated for the following four AE categories: all RTIs; signs and symptoms potentially indicating RTI; lower RTI; and pneumonia. RESULTS: Thirty-one studies were identified, in which 16 583 patients received esomeprazole and 12 044 patients received either placebo or comparator acid-suppressive drugs. The occurrence of all four categories of AEs was similar between esomeprazole and placebo (all RTIs: 9.2% versus 8.5%; signs and symptoms of RTI: 1.8% versus 1.8%; lower RTI: 1.6% versus 1.5%; and pneumonia: 0.2% in both groups). The RR estimates were as follows: all RTIs, 0.93 (99% CI 0.78, 1.11); signs and symptoms of RTI, 0.85 (99% CI 0.57, 1.27); lower RTI, 0.92 (99% CI 0.59, 1.42); and pneumonia, 0.94 (99% CI 0.29, 3.07). The distribution of RTIs by patient sex and age showed a similar pattern in esomeprazole and placebo-treated patients. The comparisons of esomeprazole with the other comparator acid-suppressive drugs showed a similar pattern with only minor numerical differences in the occurrence of RTI between the drugs. There were no significant between-group differences with esomeprazole versus placebo for all four categories of AEs according to esomeprazole dosage, treatment indication and duration of treatment. CONCLUSIONS: This pooled analysis found no causal association between acid-suppressive therapy with esomeprazole and increased risk of community-acquired RTI, including pneumonia, in patients receiving this agent for gastric acid-related disorders.
J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Jun 12;
Hishinuma T, Suzuki K, Yamaguchi H, Yamagishi H, Koike T, Ohara S, Shimosegawa T, Mano N, Goto J
A rapid, simple and highly sensitive method was developed for the quantitative determination of lansoprazole and rabeprazole concentrations in 20muL of human serum using high-performance liquid chromatography/tandem mass spectrometry (LC/MS/MS). Analytes, along with an internal standard (lansoprazole deuterium derivatives), were separated using a mobile phase of acetonitrile/1mM ammonium formate (140/60, v/v) on a C18 analytical column and analyzed in the selected reaction-monitoring (SRM) mode. The lower limit of quantification was 0.25ng/mL. A good linear response was observed for each analyte (from 0.25ng to 2.5mug/mL). This method was useful for therapeutic drug monitoring and pharmacokinetic studies.
Linear mucosal defect may be characteristic of lansoprazole-associated collagenous colitis.
Gastrointest Endosc. 2008 Jun; 67(7): 1185-91
Umeno J, Matsumoto T, Nakamura S, Jo Y, Yada S, Hirakawa K, Yoshimura R, Yamagata H, Kudo T, Hirano A, Gushima M, Yao T, Nakashima Y, Iida M
BACKGROUND: Although some cases of collagenous colitis have been induced by lansoprazole (LPZ), the clinicopathologic features of LPZ-associated collagenous colitis have not been elucidated. OBJECTIVE: To elucidate the clinical, endoscopic, and histopathologic features of LPZ-associated collagenous colitis. DESIGN: Retrospective case study. PATIENTS: The subjects were 13 patients with collagenous colitis diagnosed during a period from 2002 to 2007. MAIN OUTCOME MEASUREMENTS: The colonoscopic and histopathologic findings were compared retrospectively between 9 cases of LPZ use (LPZ group) and 4 cases without the use of LPZ (non-LPZ group). RESULTS: A colonoscopy revealed a linear mucosal defect more frequently in the LPZ group (7 of 9 cases [78%]) than in the non-LPZ group (0 of 4 cases [0%], P = .02). Friable mucosa was also noted in 4 patients (44%) in the LPZ group but none in the non-LPZ group. The colonoscopic finding in the non-LPZ group was either normal mucosa or nonspecific minimal abnormalities, whereas patients in the LPZ group had either a linear mucosal defect, mucosal bleeding, or both (P = .001). On histologic examination, the subepithelial collagen band was thicker in patients in the LPZ group than in those in the non-LPZ group (median 45 vs 26.3 mum). All patients in the LPZ group recovered from diarrhea after discontinuance of LPZ. LIMITATION: A small number of patients. CONCLUSIONS: Linear mucosal defects and friable mucosa may be characteristic colonoscopic findings in cases of LPZ-associated collagenous colitis.
Anticholinergic Activity of 107 Medications Commonly Used by Older Adults.
J Am Geriatr Soc. 2008 May 26;
Chew ML, Mulsant BH, Pollock BG, Lehman ME, Greenspan A, Mahmoud RA, Kirshner MA, Sorisio DA, Bies RR, Gharabawi G
The objective of this study was to measure the anticholinergic activity (AA) of medications commonly used by older adults. A radioreceptor assay was used to investigate the AA of 107 medications. Six clinically relevant concentrations were assessed for each medication. Rodent forebrain and striatum homogenate was used with tritiated quinuclidinyl benzilate. Drug-free serum was added to medication and atropine standard-curve samples. For medications that showed detectable AA, average steady-state peak plasma and serum concentrations (C(max)) in older adults were used to estimate relationships between in vitro dose and AA. All results are reported in pmol/mL of atropine equivalents. At typical doses administered to older adults, amitriptyline, atropine, clozapine, dicyclomine, doxepin, L-hyoscyamine, thioridazine, and tolterodine demonstrated AA exceeding 15 pmol/mL. Chlorpromazine, diphenhydramine, nortriptyline, olanzapine, oxybutynin, and paroxetine had AA values of 5 to 15 pmol/mL. Citalopram, escitalopram, fluoxetine, lithium, mirtazapine, quetiapine, ranitidine, and temazepam had values less than 5 pmol/mL. Amoxicillin, celecoxib, cephalexin, diazepam, digoxin, diphenoxylate, donepezil, duloxetine, fentanyl, furosemide, hydrocodone, lansoprazole, levofloxacin, metformin, phenytoin, propoxyphene, and topiramate demonstrated AA only at the highest concentrations tested (patients with above-average C(max) values, who receive higher doses, or are frail may show AA). The remainder of the medications investigated did not demonstrate any AA at the concentrations examined. Psychotropic medications were particularly likely to demonstrate AA. Each of the drug classifications investigated (e.g., antipsychotic, cardiovascular) had at least one medication that demonstrated AA at therapeutic doses. Clinicians can use this information when choosing between equally efficacious medications, as well as in assessing overall anticholinergic burden.
BMC Gastroenterol. 2008; 8: 18
Wilcox CM, Martin T, Phadnis M, Mohnen J, Worthington J, Hirschowitz BI
BACKGROUND: The relationship between proton pump inhibitor therapy and other acid suppressing medications and the risk of gastrointestinal infections remains controversial. METHODS: Patients enrolled in a long-term trial of lansoprazole for Zollinger-Ellison syndrome and other acid hypersecretory states had interval histories taken every six months regarding hospitalizations or other intercurrent medical conditions. All medications taken were also reviewed at each visit. In addition, available patients were specifically queried during the study period 2006-2007 regarding the development of any gastrointestinal infections, hospitalizations, and prescriptions for antibiotics. RESULTS: Ninety patients were enrolled in our long-term study and 81 were available for review. The median basal gastric pH for the cohort after stabilization on therapy was 2.9 and ranged from 1.1 - 8.4 with a median pentagastrin stimulated gastric pH of 1.60 (range 1.0 - 8.2). No patient developed a clinically significant gastrointestinal infection during the study. The median patient years of follow-up were 6.25 years. CONCLUSION: In a cohort of patients with gastric acid hypersecretion in whom acid secretion status was monitored on lansoprazole, all were free of significant gastrointestinal infections on long-term follow-up. TRIAL REGISTRATION: NCT00204373.
Hepatogastroenterology. 2008 Jan-Feb; 55(81): 138-41
Suzuki M, Tanaka S, Suzuki K, Kitahora T, Masaoka T, Suzuki H, Hibi T
BACKGROUND/AIMS: To examine the influence of long-term treatment of H. pylori-infected patients with proton pump inhibitors (PPI) on the toxic oxidant production in the stomach. METHODOLOGY: Eight H. pylori-positive patients with gastric ulcer were enrolled, and tissue samples were obtained endoscopically from the antrum and corpus. The tissue contents of neutrophil myeloperoxidase (MPO) and oxygen-derived free radicals were quantified by ELISA and chemiluminescence (ChL) assay. The H. pylori density in the tissue specimens was scored by immunohistochemistry and the mucosal infiltration by neutrophils and monocytes was scored by histopathology. The effects of PPI on these parameters were evaluated by oral administration of lansoprazole (LPZ) at the dose of 30mg od for 8 weeks, followed by 15mg for 24 weeks. RESULTS: Eight-week treatment with LPZ significantly increased the corpus ChL by 400%, which remained unchanged at this level during the subsequent 24 weeks, but the antrum ChL decreased slightly following LPZ-treatment. No significant changes in the mucosal MPO activity or the histologically determined parameters of H. pylori density and neutrophil/monocyte infiltration were observed in either portion of the stomach. CONCLUSIONS: The mucosal oxidative stress level significantly increased in the corpus mucosa after long-term treatment with LPZ, which may be independent of inflammatory cell infiltration.
Presse Med. 2008 May 23;
Mouly S, Charlemagne A, Le Jeunne P, Fagnani F
AIMS: Proton pump inhibitors (PPIs) rank third among drug classes in the amount they cost the French health care system annually (more than a billion euros, i.e., 5.7% of community pharmaceutical expenditures, 50% prescribed for gastroesophageal reflux disease (GERD)). METHODS: Data for a representative sample of patients aged 20 years and older, who visited their GP at least once in 2005 for uncomplicated symptomatic GERD came from the Thales database (1200 representative general practitioners (GP) connected to a computerized network) a. RESULTS: In 2005, 122 571 patients (mean age, 56 years, 45% male, 2.6 consultations for GERD) met the inclusion criteria. Extrapolated to the French population, this sample corresponds to 5.7 million people, i.e., 13% of the adult population who visited a GP during the year. PPIs were prescribed as first-line treatment for GERD in 84% of the consultations. Omeprazole, as a proprietary or generic drug, was prescribed most often (79%) and at a full dose (20mg), while other compounds (lansoprazole, pantoprazole, rabeprazole and esomeprazole) were prescribed at half dose in 64% of cases. The extrapolated annual cost of PPIs reimbursed for this indication was 465 million euros (Meuro) at a mean reimbursement level of 73%. Brand-name omeprazole still accounts for 11% of the total cost reimbursed. Complete replacement of brand-name omeprazole by its generic counterpart would reduce costs by 18.35Meuro (-4.3% reimbursed expenditure). The switch from generic full-dose omeprazole to a half dose of other PPIs would allow a further saving of 2.6 (with lansoprazole) to 13.2 Meuro (with pantoprazole). CONCLUSION: A substantial saving in reimbursed pharmaceutical spending in uncomplicated GERD and full compliance with clinical practice recommendations could be achieved by the substitution of less expensive PPIs.
Biochem Pharmacol. 2008 Jul 1; 76(1): 139-45
Yoshinari K, Ueda R, Kusano K, Yoshimura T, Nagata K, Yamazoe Y
Omeprazole induces human CYP1A1 and CYP1A2 in human hepatoma cells and human liver. Aryl hydrocarbon receptor (AHR) is shown to be involved in this induction. However, its precise molecular mechanism remains unknown because the chemical activates AHR without its direct binding in contrast to typical AHR ligands such as 3-methylcholanthrene (3MC) and beta-naphthoflavone (BNF). Human CYP1A1 and CYP1A2 genes are located in a head-to-head orientation sharing about 23 kb 5'-flanking region. Recently, we succeeded to measure CYP1A1 and CYP1A2 transcriptional activities simultaneously using dual reporter gene constructs containing the 23 kb sequence. In this study, transient transfection assays have been performed using numbers of single and dual reporter constructs to identify omeprazole-responsive region for CYP1A1 and CYP1A2 induction. Reporter assays with deletion constructs have demonstrated that the omeprazole-induced expression of both CYP1A1 and CYP1A2 is mediated via the common regulatory region containing multiple AHR-binding motifs (the nucleotides from -464 to -1829 of human CYP1A1), which is identical with the region for BNF and 3MC induction. Interestingly, omeprazole activated the transcription of CYP1A1 and CYP1A2 to similar extents while BNF and 3MC preferred CYP1A1 expression. We have also found that primaquine is an omeprazole-like CYP1A inducer, while lansoprazole and albendazole are 3MC/BNF-like in terms of the CYP1A1/CYP1A2 preference. The present results suggest that omeprazole as well as BNF and 3MC activates both human CYP1A1 and CYP1A2 expression through the common regulatory region despite that omeprazole may involve a different cellular signal(s) from BNF and 3MC.
Evaluation of Antibiotic Therapy for Eradication of "Candidatus Helicobacter heilmannii"
Antimicrob Agents Chemother. 2008 May 19;
Matsui H, Aikawa C, Sekiya Y, Takahashi S, Murayama SY, Nakamura M
A triple-agent therapy with lansoprazole (15 mg/kg)-clarithromycin (50 mg/kg)-amoxicillin (50 mg/kg) twice daily for seven days fully cleared "Candidatus Helicobacter heilmannii" from infected mouse stomachs. Moreover, gastric mucosa-associated lymphoid tissue (MALT) lymphoma-like lesions in the stomach had nearly disappeared in treated mouse four months after the therapy.
A review of rabeprazole in the treatment of acid-related diseases.
Ther Clin Risk Manag. 2007 Jun; 3(3): 363-79
Pace F, Pallotta S, Casalini S, Porro GB
Rabeprazole is a proton pump inhibitor. Pharmacodynamic data show rabeprazole can achieve optimal acid suppression since the first administration and can maintain this advantage in the following days of therapy. Moreover, rabeprazole has the highest pKa (~ 5.0, the pH at which a drug becomes 50% protonated), and hence the molecule can be activated at higher pH levels much faster than other PPIs. Due to its peculiar catabolic pathway, ie, a prevalent metabolism through a non-enzymatic pathway, rabeprazole is less susceptible to the influence of genetic polymorphisms for CYP2C19, resulting in minor influences on its pharmacokinetics and pharmacodynamics. In terms of clinical efficacy, rabeprazole 20 mg uid or 10 mg bid produced healing rates at 8 weeks similar to those obtained with omeprazole 20 mg uid in erosive esophagitis patients, and in NERD patients doses of 10 or 20 mg are equivalent and both are better than placebo at 2 and 4 weeks. To prevent symptomatic relapse, on-demand strategy with rabeprazole 10 mg daily appears to be ideal, due to its rapidity of onset; results on NERD patients have documented its superiority over placebo. Continuous treatment, however, up to 5 years, seems to achieve better results than on-demand therapy, particularly in patients with esophagitis. It is debated whether in the latter halved doses (10 mg) are really equivalent to full dose (20 mg). Rabeprazole has been used with success in the treatment of some atypical GERD manifestations, such as dysphagia associated with GERD, GERD-related asthma and chest-pain, and in the therapy of Barrett's esophagus. Finally, rabeprazole achieves similar Helicobacter pylori eradication rates compared with omeprazole and lansoprazole when co-administrated with low or high doses of antibiotics (amoxicillin and clarithromycin). In addition, low doses of rabeprazole (10 mg/bid) may be effective in eradicating the pathogen.