Prevacid
Determination of lansoprazole and two of its metabolites by liquid-liquid extraction and automated column-switching high-performance liquid chromatography: application to measuring CYP2C19 activity.

Uno T, Yasui-Furukori N, Takahata T, Sugawara K, Tateishi T.

Department of Pharmacy, Hirosaki University Hospital, Hirosaki, Japan.

A simple and sensitive column-switching high-performance liquid chromatographic (HPLC) method for the simultaneous determination of lansoprazole, a proton pump inhibitor and its major metabolites: 5-hydroxylansoprazole and lansoprazole sulfone in human plasma. The test compounds were extracted from 1 mL of plasma using diethyl ether-dichloromethane (7:3, v/v) mixture and the extract was injected into a column I (TSK-PW precolumn, 10 microm, 3.5 mm x 4.6 mm i.d.) for clean-up and column I (C(18) STR ODS-II analytical column, 5 microm, 150 mm x 4.6 mm i.d.) for separation. The peak was detected by a ultraviolet detector set at a wavelength of 285 nm, and the total time for a chromatographic separation was approximately 25 min. The method was validated for the concentration range from 3 to 5000 ng/mL. Mean recoveries were 74.0% for lansoprazole, 68.3% for 5-hydroxylansoprazole, and 79.4% for lansoprazole sulfone. Intra- and inter-day relative standard derivatives were less than 6.1 and 5.1% for lansoprazole, 5.8 and 5.8% for 5-hydroxylansoprazole, 4.4 and 5.9% for lansoprazole sulfone, respectively, at the different concentration ranges. This method is suitable for use in therapeutic drug monitoring and pharmacokinetic studies, and provides use tool for measuring CYP2C19 activity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15664363&dopt=Abstract lansoprazole Prevacid



Prevacid
The safety of proton pump inhibitors in pregnancy: a multicentre prospective controlled study.

Diav-Citrin O, Arnon J, Shechtman S, Schaefer C, van Tonningen MR, Clementi M, De Santis M, Robert-Gnansia E, Valti E, Malm H, Ornoy A.

The Israeli Teratogen Information Service, Israel Ministry of Health, Jerusalem, Israel.

BACKGROUND: Proton pump inhibitors are used to treat gastro-oesophageal reflux and peptic ulcers. Gastro-oesophageal reflux is a common condition in pregnancy. Human pregnancy experience with lansoprazole or pantoprazole is very limited. More data exist on the safety of omeprazole in pregnancy. AIM: To assess the safety of proton pump inhibitors in pregnancy. METHODS: The rate of major anomalies was compared between pregnant women exposed to omeprazole, lanzoprazole, or pantoprazole and a control group counselled for non-teratogens. The study design is a multicentre (n = 8), prospective, controlled study of the European Network of Teratology Information Services. RESULTS: We followed up 295 pregnancies exposed to omeprazole [233 in the first trimester (T1)], 62 to lansoprazole (55 in T1) and 53 to pantoprazole (47 in T1), and compared pregnancy outcome to that of 868 European Network of Teratology Information Services controls. The rate of major congenital anomalies did not differ between the exposed and control groups [omeprazole nine of 249 (3.6%), lansoprazole two of 51 (3.9%) and pantoprazole one of 48 (2.1%) vs. controls 30 of 792 = 3.8%]. No differences were found when exposure was limited to the first trimester after exclusion of genetic, cytogenetic or infectious anomalies. CONCLUSIONS: This study suggests that proton pump inhibitors do not represent a major teratogenic risk in humans.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15691301&dopt=Abstract lansoprazole Prevacid



Prevacid
Efficacy of esomeprazole 40 mg vs. lansoprazole 30 mg for healing moderate to severe erosive oesophagitis.

Fennerty MB, Johanson JF, Hwang C, Sostek M.

Oregon Health & Science University, Portland, OR 97239-3098, USA. fannerty ohsu.edu

BACKGROUND: Secondary analyses from previous studies indicated that esomeprazole was more effective than lansoprazole and omeprazole in healing moderate or severe (Los Angeles grades C or D) erosive oesophagitis (EE). AIM: To compare prospectively healing rates with esomeprazole vs. lansoprazole in patients with moderate to severe EE. METHODS: In this multicentre, randomized, double-blind, parallel-group trial, adult patients with endoscopically confirmed moderate or severe EE received esomeprazole 40 mg (n = 498) or lansoprazole 30 mg (n = 501) once daily for up to 8 weeks. The primary end point was EE healing through week 8. Secondary assessments included investigator-assessed resolution of symptoms and safety and tolerability. RESULTS: Time to healing was significantly different (P = 0.007), favouring esomeprazole. Estimated healing rates at week 8 were 82.4% with esomeprazole 40 mg and 77.5% with lansoprazole 30 mg. Heartburn resolved at week 4 in 72% and 64% of patients who received esomeprazole and lansoprazole, respectively (P = 0.005). Control of other GERD symptoms was similar between treatments. Both treatments were well tolerated. CONCLUSIONS: With 8 weeks' treatment, esomeprazole 40 mg once daily heals moderate to severe EE faster and in more patients, and resolves heartburn in more patients after 4 weeks of treatment, than lansoprazole 30 mg once daily.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15709997&dopt=Abstract lansoprazole Prevacid



Prevacid
Concomitant dosing of famotidine with a triple therapy increases the cure rates of Helicobacter pylori infections in patients with the homozygous extensive metabolizer genotype of CYP2C19.

Okudaira K, Furuta T, Shirai N, Sugimoto M, Miura S.

Second Department of Internal Medicine, National Defense Medical College, Tokorozawa, Saitama, Japan. grd1819 gr.ndmc.ac.jp

BACKGROUND: Proton-pump inhibitors, such as lansoprazole, are metabolized in the liver by CYP2C19 and cannot inhibit acid sufficiently in homozygous extensive metabolizers of CYP2C19. AIM: To examine whether famotidine would increase the cure rates of Helicobacter pylori infection by a standard triple therapy. METHODS: A total of 177 H. pylori-positive patients were randomly assigned to either lansoprazole 30 mg b.d., clarithromycin 200 mg b.d. and amoxicillin 750 mg b.d. for 1 week (LCA group; n = 89) or famotidine 20 mg b.d., lansoprazole 30 mg b.d., clarithromycin 200 mg b.d. and amoxicillin 750 mg b.d. for 1 week (FLCA group; n = 88). Famotidine was administered after lunch and before sleep, and the others were after breakfast and dinner. CYP2C19 genotypes were determined by a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: In the LCA group, the eradication rates for homozygous extensive metabolizers, heterozygous extensive metabolizers, and poor metabolizers were 63%, 87%, and 100%, respectively (P = 0.014). Those in the FLCA group were 85%, 85%, and 100%, respectively (N.S.). The cure rate for homozygous extensive metabolizers in the FLCA group was significantly higher than that in the LCA group (P = 0.035). CONCLUSION: Famotidine improves the cure rate of H. pylori infection by a triple therapy in CYP2C19 homozygous extensive metabolizers patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15710002&dopt=Abstract lansoprazole Prevacid



Prevacid
Antimicrobial actions of benzimidazoles against oral streptococci.

Nguyen PT, Baldeck JD, Olsson J, Marquis RE.

Department of Microbiology & Immunology and Center for Oral Biology, University of Rochester Medical Center, Rochester, NY 14642-8672, USA.

Nguyen PTM, Baldeck JD, Olsson J, Marquis RE. Antimicrobial actions of benzimidazoles against oral streptococci. Oral Microbiol Immunol 2005: 20: 93-100. (c) Blackwell Munksgaard, 2005.Background/aim: Benzimidazoles, such as lansoprazole and omeprazole, are used extensively as proton-pump inhibitors to control stomach acid secretion and also have antimicrobial actions against Helicobacter pylori. Our objective was to determine whether they are potentially useful antimicrobials against oral bacteria. Methods: Streptococcus mutans was our main test organism. It was grown in suspension cultures and biofilms. Standard physiologic assays were used to assess inhibitory actions of benzimidazoles. Results: Benzimidazoles inhibited acid production by S. mutans in suspensions or biofilms. In pH-drop experiments, lansoprazole at a level of only 0.025 mm irreversibly inhibited acid production from glycolysis. Cell uptake of lansoprazole was found to be very pH sensitive and occurred mainly at pH values below about 5, indicating that the protonated form was taken up. Lansoprazole inhibition of glycolysis could be blocked by 2-mercaptoethanol, which suggests that disulfide bonds form between benzimidazoles and protein targets. Identified targets for benzimidazole inhibition included the phosphoenolpyruvate : sugar phosphotransferase system, the glycolytic enzymes aldolase, glyceraldehyde-3-phosphate dehydrogenase, and lactic dehydrogenase, and enzymes such as urease and arginine deiminase. Lansoprazole increased proton permeabilities of S. mutans cells but did not inhibit F-ATPases. Although cells in biofilms were somewhat less sensitive to the agents than those in suspensions, biofilm glycolysis was still markedly inhibited by 0.1 mm lansoprazole. Benzimidazoles are bactericidal, and the oral anaerobes Fusobacterium nucleatum and Prevotella intermedia were more sensitive to killing than was S. mutans. Conclusion: Benzimidazoles appear to be useful inhibitors of oral bacteria in acid environments such as progressing caries lesions.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15720569&dopt=Abstract lansoprazole Prevacid