Prevacid
Effect of water intake on pharmacokinetics of lansoprazole from fast disintegrating tablet in human subjects.

Iwasaki K, Ito Y, Shibata N, Takada K, Sakurai Y, Takagi N, Irie S, Nakamura K.

Department of Pharmacokinetics, Kyoto Pharmaceutical University, 5-Misasagi-Nakauchicho, Yamashina-ku, Kyoto, Japan. Iwasaki_Kouji takeda.co.jp

Lansoprazole fast disintegrating tablet (LFDT) has been developed as a multiple unit formulation to increase the QOL of patients, i.e., easy intake without water. However, there is a possibility that patients intake LFDT in accordance with clarithromycin and amoxicillin with water. To study the effect of water on the absorption of lansoprazole (LPZ), the study was carried out using human volunteers. After selected by phenotype of LPZ metabolism, extensive metabolizers (EMs) of LPZ were used in this study. Twelve healthy male EMs intook LFDT containing 30 mg LPZ with 150 mL of water and without-water, i.e., with saliva, to study the pharmacokinetics of LPZ from the gastrointestinal tract by a cross-over manner with one-week washout period under fasted condition in the morning. The mean AUC(0-24s) were 2004.4+/-973.6 ng.h/mL in without-water experiment and 2018.5+/-1159.6 ng.h/mL in the case of with-water experiment. Mean C(maxs) were 851.9+/-450.8 ng/mL in without-water experiment and 830.8+/-456.8 ng/mL in with-water experiment, respectively. ANOVA was applied to the log-transformed AUC(0-24) and C(max) values. The 90% two sided confidence intervals for log-transformed AUC(0-24) was 0.78-1.22 and that for log-transformed C(max) was 0.67-1.37, respectively. By comparing these pharmacokinetic parameters, we may state that there was no significant difference between the two administration modes.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15548851&dopt=Abstract lansoprazole Prevacid



Prevacid
Efficacy of metronidazole for the treatment of clarithromycin-resistant Helicobacter pylori infection in a Japanese population.

Shimoyama T, Fukuda S, Mikami T, Fukushi M, Munakata A.

First Department of Internal Medicine, Hirosaki University School of Medicine, 5 Zaifu-cho, 036-8562, Hirosaki, Japan.

BACKGROUND: Eradication of Helicobacter pylori has become a common treatment for several diseases. There is an increase in antibiotic-resistant strains, which causes the failure of eradication. The aim of this study was to investigate the usefulness of metronidazole for the treatment of H. pylori infection in patients who failed eradication therapy. METHODS: Seventy H. pylori-positive patients who had failed eradication treatment with first-line triple therapy, which consisted of a proton pump inhibitor, amoxicillin, and clarithromycin, were enrolled into the study. Before the second-line therapy, patients underwent endoscopy to obtain H. pylori strains to test susceptibility to antibiotics. Lansoprazole (30 mg b.d.), amoxicillin (750 mg b.d.), and metronidazole (250 mg b.d.) were administered for 1 week, and the result was tested by 13C-UBT. RESULTS: H. pylori was isolated from 62 patients, and 52 of them (83.9%) were clarithromycin resistant. There was no amoxicillin- or metronidazole-resistant strain. No major adverse effects were seen, and all the patients completed the 1-week regimen. The eradication rates of lansoprazole-amoxicillin-metronidazole were 96.2% (51/53; 95% CI, 87.0%-99.5%) using both intention-to-treat analysis and per protocol analysis. CONCLUSIONS: Lansoprazole-amoxicillin-metronidazole triple therapy is an effective and promising second-line H. pylori eradication therapy in a north Japanese population, which has a low frequency of metronidazole resistance.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15549444&dopt=Abstract lansoprazole Prevacid



Prevacid
Fatal toxic epidermal necrolysis due to lansoprazole.

Heaton NR, Edmonds EV, Francis ND, Bunker CB, Bowling JC, Morar N.

Department of Dermatology, Chelsea and Westminster Hospital, London, UK.

Toxic epidermal necrolysis (TEN) is a serious cutaneous reaction and is most commonly drug induced. It is associated with significant morbidity and mortality. We describe a patient who developed fatal TEN after re-exposure to lansoprazole. Three years previously he presented with erythema multiforme due to the same drug. To our knowledge this is the first published report of TEN occurring with lansoprazole.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15550134&dopt=Abstract lansoprazole Prevacid



Prevacid
Effect of sucralfate on antibiotic therapy for Helicobacter pylori infection in mice.

Watanabe K, Murakami K, Sato R, Kashimura K, Miura M, Ootsu S, Miyajima H, Nasu M, Okimoto T, Kodama M, Fujioka T.

Department of Infectious Diseases, Faculty of Medicine, Oita University, Oita, Japan. kwata med.oita-u.ac.jp

It has been documented that sucralfate, a basic aluminum salt, enhances the efficacies of antibiotics against Helicobacter pylori, resulting in eradication rates comparable to those associated with the use of proton pump inhibitors. However, its mechanism of action remains unclear. The aim of the present study was to investigate sucralfate's ability to complement antibiotic treatment of H. pylori infection in vivo. Four weeks following induced H. pylori infection, clarithromycin (CAM) and amoxicillin (AMPC) were administered orally to C57BL/6 mice for 5 days, both with and without sucralfate or lansoprazole. When sucralfate was concurrently given with CAM and AMPC at the maximum noninhibitory doses for the treatment of H. pylori infection, the bacterial clearance rates were comparable to those achieved by treatment with lansoprazole plus those antibiotics. The results of pharmacokinetic studies showed that lansoprazole delayed gastric clearance and accelerated the absorption of CAM, whereas sucralfate suppressed both gastric clearance and absorption. AMPC was undetectable in all samples. Scanning electron microscopy with a microscope to which a energy dispersive spectrometer was attached revealed that aluminum-containing aggregated substances coated the mucosa surrounding H. pylori in mice receiving sucralfate plus antibiotics, whereas the gastric surface and pits where H. pylori had attached were clearly visible in mice receiving lansoprazole plus antibiotics. The addition of sucralfate to the antibiotic suspension resulted in a more viscous mixture that bound to the H. pylori-infected mucosa and that inhibited the loss of CAM bioavailability in the acidic environment. Sucralfate delays gastric clearance of CAM and physically captures H. pylori through the creation of an adherent mucus, which leads to bacterial clearance.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15561829&dopt=Abstract lansoprazole Prevacid



Prevacid
Clinical outcome using lansoprazole in acid hypersecretors with and without Zollinger-Ellison syndrome: a 13-year prospective study.

Hirschowitz BI, Simmons J, Mohnen J.

Division of Gastroenterology and Hepatology, The University of Alabama at Birmingham, UAB Station, Birmingham, AL 35294-0007, USA. bih uab.edu

BACKGROUND & AIMS: Unremitting gastric acid and pepsin hypersecretion causes serious persistent and relapsing lesions, but the natural history with medical treatment alone has not been well-defined. The aims of this study were to heal and prevent relapse of acid/peptic lesions during acid suppression and to analyze benefits and risks during long-term lansoprazole treatment. METHODS: Sixty-seven patients (49 with Zollinger-Ellison syndrome [ZES], 18 without), with basal acid output (BAO) >15 mmol/h or >5 mmol/h if post-antrectomy (n = 9, all ZES), were treated with individually optimized doses of lansoprazole (7.5-450 mg/day; median, 75 mg/day) to reduce BAO to <5 mmol/h or <1 mmol/h post-antrectomy and underwent endoscopy every 3-6 months for up to 13 years (median, 6.25 years). RESULTS: Before treatment, 94% had duodenal ulcer, 64% had esophagitis, 60% had 1 or more bleeding episodes, 13% had perforated ulcers, 90% had pain, 60% had heartburn, and 40%-48% had diarrhea, vomiting, and/or weight loss. Forty-seven patients (70%) remained symptom- and lesion-free, whereas 13 (20%) had mild, transient relapses, and 7 (10%) had more complicated relapses. Overall, symptoms were reduced 90+%; ulcer or esophagitis relapsed in 4.8% of patients/year, unrelated to Helicobacter pylori , whereas complications declined to <2%/y. Post-antrectomy ZES patients had 3.6-fold higher relapse rates than unoperated ZES patients (67% vs 18%, respectively). With BAO >5 mmol/h in intact patients, relative risk of relapse was 4.1, confidence interval 2.1-8.1, P < .001. Twenty patients died, 3 as a result of ZES (2 metastatic gastrinomas). CONCLUSIONS: With individually optimized medical suppression of acid secretion, 90% of patients had good to excellent long-term outcomes without surgery, with an annualized total relapse rate of <5%.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15645403&dopt=Abstract lansoprazole Prevacid