Prevacid
Comparison of ranitidine and lansoprazole in short-term low-dose triple therapy for Helicobacter pylori infection.

Kihira K, Satoh K, Saifuku K, Taniguchi Y, Takimoto T, Yamamoto H, Ido K, Yoshida Y, Kimura K.

Department of Gastroenterology, Jichi Medical School, Kawachi-gun, Japan.

AIM: To evaluate the efficacy and safety of two 1-week low-dose triple-therapy drug regimens involving antisecretory drugs for Helicobacter pylori infection. 99 patients with H. pylori infection were treated with either lansoprazole or ranitidine used together with clarithromycin and metronidazole. METHODS: The drug combination and administration periods in the proton pump inhibitor group were lansoprazole 30 mg o.m., clarithromycin 200 mg b.d. and metronidazole 250 mg b.d., all given for 7 days (LCM group). The ranitidine group received ranitidine 150 mg b.d., clarithromycin 200 mg b.d. and metronidazole 250 mg b.d. also for 7 days (RCM group). The presence or absence of H. pylori was determined from gastric biopsy specimens taken from both the antrum and the body, by smear, culture and tissue section (Giemsa stain). Cure was defined as failure to find evidence of H. pylori infection 4 weeks after antimicrobial therapy had ended. RESULTS: The cure of H. pylori infection was 88% in the LCM group (44 of 50; 95% confidence interval (CI) = 79-97%) and 92% in the RCM group (45 of 49; 95% CI = 84-99%). The incidence of adverse events was 16% and 18% for the two groups, respectively. CONCLUSIONS: No significant differences in cure rate and safety profiles were noted between the two regimens, suggesting that moderate acid inhibition using an H2-blocker is sufficient to achieve optimal H. pylori eradication.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9218074&dopt=Abstract lansoprazole Prevacid



Prevacid
Evaluation of omeprazole and lansoprazole as inhibitors of cytochrome P450 isoforms.

Ko JW, Sukhova N, Thacker D, Chen P, Flockhart DA.

Department of Medicine, Georgetown University Medical Center, Washington, DC 20007, USA.

The human clearance of omeprazole and lansoprazole is conducted primarily by the hepatic cytochrome P450 (CYP) system. Efficacy data indicate few differences between these two drugs, but they may exhibit discrete drug interaction profiles. To compare the potency and specificity of these drugs as inhibitors of CYP isoforms, we performed in vitro studies with human liver microsomal preparations. Both drugs were potent, competitive inhibitors of CYP2C19, as measured by the conversion of S-mephenytoin to 4-hydroxymephenytoin (k(i) = 3.1 +/- 2.2 microM for omeprazole, K(i) = 3.2 +/- 1.3 microM for lansoprazole). For omeprazole, the highest concentration at which >70% inhibition of CYP2C19 was observed with no significant inhibitory effect on other isoforms was at least 20 times greater than K(i). Both drugs were competitive inhibitors of CYP2C9-catalyzed conversion of tolbutamide to 4-hydroxytolbutamide (K(i) = 40.1 +/- 14.8 microM for omeprazole, K(i) = 52.1 +/- 1.4 microM for lansoprazole) and were noncompetitive inhibitors of CYP3A-catalyzed conversion of dextromethorphan to 3-methoxymorphinan (K(i) = 84.4 +/- 4.0 microM for omeprazole, K(i) = 170.4 +/- 7.1 microM for lansoprazole). Lansoprazole was at least 5 times more potent (K(i) = 44.7 +/- 22.0 microM) than omeprazole (k(i) = 240.7 +/- 102.0 microM) as an inhibitor of CYP2D6-mediated conversion of dextromethorphan to dextrorphan. No inhibition of CYP1A2, assessed by measuring the conversion of phenacetin to acetaminophen, was noted. Our data suggest that whereas the inhibitory profiles of these two drugs are similar, lansoprazole may be the more important in vitro inhibitor of CYP2D6. Since its inhibition is very potent and has a broad "window of selectivity," omeprazole seems to be a useful, selective inhibitor of CYP2C19.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9224780&dopt=Abstract lansoprazole Prevacid



Prevacid
Genetic polymorphism of CYP2C19 and lansoprazole pharmacokinetics in Japanese subjects.

Katsuki H, Nakamura C, Arimori K, Fujiyama S, Nakano M.

Department of Pharmacy, Kumamoto University Hospital, Japan.

OBJECTIVE: We investigated whether interindividual differences in the pharmacokinetic disposition of lansoprazole are attributed to the genetic polymorphism of CYP2C19 which occurred by two mutations. CYP2C19m1 and CYP2C19m2, in 20 Japanese subjects. METHODS: Polymerase chain reaction (PCR) restriction fragment length polymorphism procedures were used to detect the CYP2C19m1 mutation in exon 5 and the CYP2C19m2 mutation in exon 4 using SmaI and BamHI, respectively. RESULTS: Ten subjects were homozygous (wt/wt subjects) for the wt allele in both exon 5 and exon 4, four subjects were heterozygous (wt/m1) for the CYP2C19m1 mutation, and two subjects were heterozygous (wt/m2) for the CYP2C19m2. The remaining four subjects had both mutated alleles in CYP2C19 genes, i.e., two were homozygous (m1/m1) for the defect in exon 5 and two were heterozygous (m1/m2) for the two defects in exons 5 and 4. The subjects in group 1 (wt/wt, wt/m1 and wt/m2) were the extensive metabolizers (EMs) for 5-hydroxylation of lansoprazole and were in the range of hydroxylation indexes from 3.83 to 19.8, whereas the subjects in group 2 (m1/m1 and m1/m2) were the poor metabolizers (PMs) and the indexes were in the range of 38.5 to 47.6. In group 2, AUC, t1/2 and CL/f of lansoprazole were significantly greater, longer, and lower, respectively, than those in group 1.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9272410&dopt=Abstract lansoprazole Prevacid



Prevacid
Localization of [14C]clarithromycin in rat gastric tissue when administered with lansoprazole and amoxicillin.

Endo H, Yoshida H, Ohmi N, Ohta K, Higuchi S, Suga T.

Department of Drug Metabolism, Research Center, Taisho Pharmaceutical Co., Ltd, 403 Yoshino-cho 1-chome, Saitama-shi, Saitama 330-8530, Japan. hiromi.endou po.rd.taisho.co.jp

After oral and intravenous administration of [14C]clarithromycin to rats, c. 60-70% of the radioactivity in the gastric tissue was found to be distributed in the mucosal layer. Co-administration of lansoprazole and amoxicillin had no apparent effect on this distribution pattern of [14C]clarithromycin. The amount of unchanged [14C]clarithromycin in gastric contents increased with co-administration of lansoprazole and amoxicillin. Microautoradiograms of the gastric mucosa showed that [14C]clarithromycin was highly distributed in the mucous layer and in surface epithelial cells following oral administration. Homogeneous distribution of radioactivity was evident in the fundic gland. With iv administration, [14C]clarithromycin seemed to be secreted by both secreting cells in the gland base and surface epithelial cells.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12161414&dopt=Abstract lansoprazole Prevacid



Prevacid
Impact of proton pump inhibitor utilization patterns on gastroesophageal reflux disease-related costs.

Hall J, Dodd S, Durkin M, Sloan S.

OBJECTIVE: To determine proton pump inhibitor (PPI) treatment patterns and their effect on costs related to gastroesophageal reflux disease. METHODS: This study used claims data to identify continuously enrolled subjects diagnosed with gastroesophageal reflux disease (GERD) and newly treated with a PPI between Oct. 1, 1999 and March 31, 2000. Data were analyzed for 6 months following PPI initiation. Results were stratified by first PPI filled during the study period. Compliance (as measured by a medication-possession ratio), dosage escalation (> 25 percent of initial dose), and daily average consumption (DACON) were measured. Regression analysis was performed on GERD-related costs using treatment patterns, type of PPI drug, and compliance as independent variables of interest. RESULTS: Of 75,452 subjects, there were 51,232 (67.9 percent) lansoprazole, 22,829 (30.3 percent) omeprazole, and 1,391 (1.8 percent) rabeprazole subjects. The possession ratio was not significantly different by drug. Only 3.5 percent of rabeprazole subjects escalated versus 5.5 percent of omeprazole subjects and 9.3 percent of lansoprazole subjects (p = .0001). Among subjects with esophageal ulcer or hiatal hernia, rabeprazole users had a significantly lower final DACON (1.03) versus both lansoprazole (1.20) and omeprazole subjects (1.22, p = .0299). Subjects who were compliant with therapy (ratio > 0.80) had 43 percent higher GERD-related pharmacy costs and 33 percent higher GERD-related total costs (both p < .001). GERD-related medical costs were not significantly affected by compliance. Subjects who filled lansoprazole prescriptions had 9.4 percent higher GERD-related pharmacy costs versus rabeprazole subjects (p < .01). Omeprazole subjects had 12.5 percent higher GERD-related total costs versus rabeprazole subjects (p < .01), while lansoprazole subjects had 18 percent higher GERD-related total costs versus rabeprazole subjects (p < .001). CONCLUSIONS: Rabeprazole subjects had lower GERD-related costs, less escalation, and lower DACON (measured as number of tablets consumed per day), compared to lansoprazole and omeprazole subjects. Compliance was not significantly different between the drugs, nor did increased compliance decrease GERD-related costs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12181872&dopt=Abstract lansoprazole Prevacid



Prevacid
A novel antioxidant and antiapoptotic role of omeprazole to block gastric ulcer through scavenging of hydroxyl radical.

Biswas K, Bandyopadhyay U, Chattopadhyay I, Varadaraj A, Ali E, Banerjee RK.

Department of Physiology, Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Kolkata 700 032, India.

The mechanism of the antiulcer effect of omeprazole was studied placing emphasis on its role to block oxidative damage and apoptosis during ulceration. Dose-response studies on gastroprotection in stress and indomethacin-induced ulcer and inhibition of pylorus ligation-induced acid secretion indicate that omeprazole significantly blocks gastric lesions at lower dose (2.5 mg/kg) without inhibiting acid secretion, suggesting an independent mechanism for its antiulcer effect. Time course studies on gastroprotection and acid reduction also indicate that omeprazole almost completely blocks lesions at 1 h when acid inhibition is partial. The severity of lesions correlates well with the increased level of endogenous hydroxyl radical (*OH), which when scavenged by dimethyl sulfoxide causes around 90% reduction of the lesions, indicating that *OH plays a major role in gastric damage. Omeprazole blocks stress-induced increased generation of *OH and associated lipid peroxidation and protein oxidation, indicating that its antioxidant role plays a major part in preventing oxidative damage. Omeprazole also prevents stress-induced DNA fragmentation, suggesting its antiapoptotic role to block cell death during ulceration. The oxidative damage of DNA by *OH generated in vitro is also protected by omeprazole or its analogue, lansoprazole. Lansoprazole when incubated in a *OH-generating system scavenges *OH to produce four oxidation products of which the major one in mass spectroscopy shows a molecular ion peak at m/z 385, which is 16 mass units higher than that of lansoprazole (m/z 369). The product shows no additional aromatic proton signal for aromatic hydroxylation in (1)H NMR. The product absorbing at 278 nm shows no alkaline shift for phenols, thereby excluding the formation of hydroxylansoprazole. The product is assigned to lansoprazole sulfone formed by the addition of one oxygen atom at the sulfur center following attack by the *OH. Thus, omeprazole plays a significant role in gastroprotection by acting as a potent antioxidant and antiapoptotic molecule.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12529378&dopt=Abstract lansoprazole Prevacid