Prevacid
Effect of lansoprazole on human leukocyte function.

Capodicasa E, De Bellis F, Pelli MA.

Institute of Internal Medicine and Oncological Sciences, Perugia University, Italy.

Recent findings on the capacity of omeprazole to influence various leukocyte functions, in vitro, raises the question on the potential use of protonic pump inhibitors, commonly used in the treatment of acid-secretion-related disorders, as immunomodulators. The aim of this study was to evaluate the in vitro effect of lansoprazole on human natural killer (NK) cell cytotoxix activity, chemotaxis and superoxide anion (O2*-) generation exerted by polymorphonucleated cells (PMNs). NK cytotoxicity activity was assessed by a 51Cr release assay, PMN chemotaxis was determined by an under agarose method and O2*- generation was analyzed on the basis of reduced cytochrome C. Incubation times with lansoprazole was 30 min for PMNs and 1-4.5 hours for NK cells, respectively. Lansoprazole induced significant dose dependent inhibition of NK cell activity and PMN functions at concentrations ranging from 100 to 1,000 microM. This study demonstrate that lansoprazole, like omeprazole, inhibits several leukocyte functions, in vitro, then suggesting that protonic pump inhibitors are able to provoke these effects, at least at certain doses.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10319286&dopt=Abstract lansoprazole Prevacid



Prevacid
The efficacy of extended-interval dosing of omeprazole in keeping gastroesophageal reflux disease patients symptom free.

Bieszk N, Kale-Pradhan PB.

Wayne State University, Detroit, MI, USA.

The potential economic advantage of alternate-day therapy for GERD maintenance must be weighed against the potential cost of failure before it can be widely instituted. The studies presented have helped develop a clinical picture of the patients who may benefit from alternate-day therapy without risk of complications or potential increases in management costs. Bank et al., reporting on a group of patients, found that patients with Grade II-IV disease had a 61% success rate at two to eight years. Bank defined success as both maintenance of endoscopic healing and symptom control. Ladas et al. found a 66.7% success rate defined as clinical and endoscopic remission in Grades II-III disease. Kurucar et al. monitored symptom control and esophageal complications in his patients and found the regimen to have a 26% success rate in Grades III-IV disease. Lind et al. found that 83% of patients could remain symptom free with on-demand therapy if they were endoscopy-negative at baseline. The results of the Mantides et al. study are important because they imply that alternate-day omeprazole therapy may be more effective than alternatives for step-down treatment, such as ranitidine or cisapride. Furthermore, patients can be educated to increase their frequency of use if symptoms should arise. Not only does this give the patient a sense of self-empowerment over his or her disease state, but it avoids the cost of switching to a PPI due to failure with an H2RA or a motility agent. Alternate-day use of omeprazole should be attempted only during the maintenance phase of GERD therapy. Patients requiring >20 mg/d to achieve healing appeared to be poor candidates for alternate-day omeprazole maintenance therapy. Based on available studies, it would seem that patients with Grades 0-II GERD would benefit most from alternate-day therapy. A role for alternate-day therapy in Grades III-IV is apparent from the results presented but requires greater caution in view of the differing success rates (26-61%) in various studies. With Grades II-III esophagitis, a mean 24-hour gastric pH >6 and a gastric pH <4 less than 10% of the time during the initial healing phase with omeprazole 20 mg/d appeared to be associated with success on alternate-day therapy. Evidence that all marketed PPIs have similar success is not available and should not be extrapolated from the data presented. Evidence that downward dosage adjustments of PPIs versus extending dosage intervals are effective in the maintenance of GERD should be recognized. Lansoprazole has been approved for treating erosive esophagitis at 30 mg/d, with the maintenance dose established at 15 mg/d. Studies showing that lansoprazole 15 mg/d is more effective than alternate-day therapy with lansoprazole 30 mg exist, although similar studies with omeprazole have not been performed. The abstracts describing the use of alternate-day omeprazole accounted for all enrollees and included endoscopic grading or pH monitoring to document disease severity at baseline. Most also included these same objective measures as end points in combination with symptom control. This strengthens the data since the positive predictive value of typical symptoms is variable. However, there are also several significant limitations. Abstracts provide only limited information on methods. All studies other than Lind et al. lacked randomization. This study was also the only one that blinded patients to their treatment. Sample sizes for the majority of the trials were quite small. Statistical analyses were not performed on any of the trial results with the exception of the trial by Lind et al. In light of the lack of evidence of statistical significance as well as study design flaws, conclusions should be drawn cautiously. Larger well-designed trials looking at both the efficacy and cost-effectiveness of alternate day omeprazole are required before a definitive recommendation can be made.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10369630&dopt=Abstract lansoprazole Prevacid



Prevacid
Effect of clarithromycin and other macrolides on the sulfoxidation and 5-hydroxylation of lansoprazole in dogs.

Masa K, Arimori K, Nakayama T, Miyamoto S, Fujii J, Nakano M.

Department of Pharmacy, Kumamoto University Hospital, Japan.

The purpose of this study was to evaluate a possible interaction between lansoprazole and clarithromycin as well as other macrolides in dogs. Lansoprazole (30 mg) was orally administered to male beagle dogs, with or without oral pretreatment with 200-mg clarithromycin twice a day for 5 d. The experiments had a randomized cross-over design with a two-week washout period between dosing regimens. Clarithromycin pretreatment for 5 d resulted in a significant increase in the area under the serum lansoprazole concentration-time curve (AUC), whereas the area for a lansoprazole metabolite, lansoprazole sulfone, was significantly reduced, as was the maximum serum concentration (Cmax) of lansoprazole sulfone. When the effects of clarithromycin on the metabolism of lansoprazole were studied using dog liver microsomes, it was found that clarithromycin significantly inhibited the formation of lansoprazole sulfone but not another metabolite, 5-hydroxylansoprazole. These results suggest that co-medication of lansoprazole with clarithromycin may produce a synergistic effect caused by the increased serum levels of lansoprazole of benefit in Helicobacter pylori eradication.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10375172&dopt=Abstract lansoprazole Prevacid



Prevacid
Combined activity of azithromycin and lansoprazole against Helicobacter pylori.

Trautmann M, Riediger C, Moricke A, Vogt K, Bohr U, Glasbrenner B.

Department of Medical Microbiology, University Hospital Ulm, Germany. matthias.trautmann medizin.uni-ulm.de

BACKGROUND: Due to its unique pharmacokinetic properties, azithromycin may be an attractive combination partner for H. pylori eradication regimens. However, up to 15% of clinical isolates are primarily resistant to azithromycin as well as to other macrolide antibiotics. Combination therapy with lansoprazole, a proton pump inhibitor known to have intrinsic antibacterial activity against H. pylori, may be useful to counteract such resistance. We therefore evaluated the combined effects of azithromycin and lansoprazole in vitro. MATERIALS AND METHODS: Minimal inhibitory concentrations (MICs) of azithromycin and lansoprazole alone and in combination were determined for 106 clinical H. pylori isolates by means of an agar dilution technique. Killing kinetics of seven isolates were also studied in fluid medium. RESULTS: MIC values for 50 and 90% of the isolates (MIC50, MIC90) were 0.19 and 0.5 mg/l for azithromycin, and 44.5 and 104 mg/l for lansoprazole. Nine strains (8.5%) had an MIC of azithromycin > or = 16 mg/l and were regarded as resistant. An additive interaction between the two drugs was found in 72 (68%), and indifferent effects in 24 strains (23%). Three of 9 azithromycin-resistant strains regained sensitivity in the presence of lansoprazole. In fluid culture, synergism between the two drugs occurred in 6 out of 7 strains tested. CONCLUSION: In the majority of strains, lansoprazole and azithromycin interacted in an additive or synergistic manner depending on the test method employed. Addition of lansoprazole restored in vitro sensitivity to azithromycin in 3 out of 9 azithromycin-resistant strains. Such effects may enhance the elimination of H. pylori during clinical eradication therapy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10382125&dopt=Abstract lansoprazole Prevacid



Prevacid
Impact of clarithromycin resistance on the effectiveness of a regimen for Helicobacter pylori: a prospective study of 1-week lansoprazole, amoxycillin and clarithromycin in active peptic ulcer.

Ducons JA, Santolaria S, Guirao R, Ferrero M, Montoro M, Gomollon F.

Digestive Disease Service, Hospital San Jorge, Huesca, Spain.

BACKGROUND: Clarithromycin is a key antimicrobial in the combinations used to cure Helicobacter pylori infections, so there is a need to define the impact of in vitro resistance on in vivo results. METHODS: A prospective trial was designed to study the effectiveness of the 1-week combination of lansoprazole, clarithromycin and amoxycillin in 102 consecutive patients with active peptic ulcer. The pre-treatment and post-treatment sensitivity to amoxycillin, metronidazole and clarithromycin were studied by E-test, and H. pylori status was defined by histology, culture and urease test at diagnosis and one month after treatment, and by urea-breath test 2 months after treatment. RESULTS: The eradication rate (intention-to-treat analysis) was 77% (95% CI: 69-86). No clinical factor was found to be different between eradicated and non-eradicated patients. Clarithromycin-resistant strains were found in 10 (10%; CI: 5-17) patients. The eradication rate was 20% (CI: 3-56) in these patients vs. 83% (CI: 75-91) in patients harbouring clarithromycin-sensitive strains (P < 0.001). A logistic-regression analysis confirmed clarithromycin resistance as the only factor associated with treatment failure. CONCLUSIONS: Clarithromycin resistance significatively impairs the effectiveness of the combination of lansoprazole, amoxycillin, and clarithromycin. The 80% efficacy goal will be difficult to reach in areas with high (>10%) primary clarithromyicin resistance, if currently recommended proton pump inhibitor-triple therapies are used.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10383507&dopt=Abstract lansoprazole Prevacid