Prevacid
[Effectiveness and safety of lansoprazole in the treatment of peptic ulcer]

[Article in Spanish]

Ramon Nogueira J, Esquivel Ayanegui F, Esquivel Rodriguez F, Saenz V, Santoyo R.

Gastroenterologo, Hospital General, SSA, Irapuato, Gto.

BACKGROUND: Lansoprazole, a new proton pump inhibitor, is now available in Mexico. It has been tested elsewhere with excellent results. AIM: To study its safety and efficacy in Mexican patients. METHOD: 40 patients with gastric or duodenal ulcer larger than 0.5 cm, from 4 hospitals in central Mexico, were included. All were subjected to a complete medical history and upper GI endoscopy. symptoms (epigastric pain, heartburn, regurgitation, nausea, vomiting) were graded 1 to 4 according to severity. Lansoprazole (one 30 mg capsule/ day) was prescribed for 4 weeks in duodenal ulcer 8 weeks in gastric ulcer. Each patient was seen once a week at the office for compliance, symptom evaluation and side effects. A second endoscopy was performed at the end of the respective treatment period. Blood (CBC, chemistries) and urine tests were performed at the beginning and end of the study. RESULTS: 23 men and 17 women were included, Mean age: 53.8 yr. (19-95). 11 gastric ulcers and 29 duodenal ulcers. 27 measured 0.6-1.5 cm; 6 ulcers measured 1.6-2.5 cm; 6 ulcers were larger than 2.5 cm. 8 patients were bleeding at admission and 4 had multiple ulcers. 2 patients were lost to follow up. symptom grading: 18 patients had 10 points or less, 21 had more than 10 points, one bleeding patient was otherwise asymptomatic. After the first week of treatment, 42% were asymptomatic, after the 2nd. week, 75% were asymptomatic and 95% at the end of the study. The second endoscopy documented complete ulcer healing in 92% out of 37 remaining patients; further lansoprazole treatment healed 2 out of three unhealed ulcers. One patient underwent surgery for duodenal bulb stenosis. Side effects were reported by 2 patients. Treatment had to be discontinued in one patient because of headache. There was no effect of lansoprazole over the laboratory tests. CONCLUSIONS: Lansoprazole was effective for prompt symptom relief in most patients and was able to heal more than 90% of gastric and duodenal ulcers with minimal side effects.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9072782&dopt=Abstract lansoprazole Prevacid



Prevacid
Lansoprazole pharmacokinetics in subjects with various degrees of kidney function.

Karol MD, Machinist JM, Cavanaugh JM.

Department of Pharmacokinetics, Abbott Laboratories, Abbott Park, IL 60064-3500, USA.

The pharmacokinetics of lansoprazole, a new benzimidazole proton pump inhibitor, was evaluated after multiple-dose oral administration to 20 subjects with various degrees of kidney function. Multiple blood samples were obtained after doses 1 and 7 of the once-daily seven-dose regimen, and plasma concentrations of lansoprazole and five metabolites were quantitated with use of HPLC. The free fraction of lansoprazole increased as kidney function declined. A significant, although weak, relationship existed between creatinine clearance (CLCR) and area under the plasma concentration versus time curve (AUC) and terminal disposition half-life (t1/2), calculated with total concentration data. Those individuals with lower CLCR values also had lower total AUC and t1/2 values. However, there was no statistically significant relationship between CLCR and peak plasma concentration or AUC, calculated with unbound concentration data. No adjustment of lansoprazole dose is recommended on the basis of impaired kidney function.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9129562&dopt=Abstract lansoprazole Prevacid



Prevacid
Effects of pantoprazole on xenobiotic metabolizing enzymes in rat liver microsomes: a comparison with other proton pump inhibitors.

Masubuchi N, Hakusui H, Okazaki O.

Drug Metabolism and Analytical Chemistry Research Laboratory, Daiichi Pharmaceutical Company, Ltd., Tokyo, Japan.

The effects of pantoprazole on xenobiotic metabolizing enzymes in rat liver microsomes were examined. Groups of female Sprague-Dawley rats were orally administered pantoprazole and other proton pump inhibitors, omeprazole and lansoprazole, at 5, 50, or 300 mg/kg/day for 7 days, followed by assays to detect changes in the levels of liver microsomal protein, cytochrome P450, cytochrome b5, NADPH cytochrome c reductase, and drug metabolizing enzyme activities. Increases in total cytochrome P450 contents were evident after a 7-day high-dose administration of all the proton pump inhibitors tested, and the increase by treatment with pantoprazole was less than that with lansoprazole. The three proton pump inhibitors increased the enzymatic activities and cytochrome P450 enzyme levels of CYP1A, CYP2B, and CYP3A. CYP1A was less induced with pantoprazole than with omeprazole or lansoprazole. In contrast, CYP2B was more strongly induced with pantoprazole than with other proton pump inhibitors. NADPH cytochrome c reductase was induced with omeprazole and pantoprazole. The present results suggest that enzyme induction differs among these proton pump inhibitors not only quantitatively but also qualitatively.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9152597&dopt=Abstract lansoprazole Prevacid



Prevacid
In-vitro activity of lansoprazole against Helicobacter pylori.

Figura N, Crabtree JE, Dattilo M.

Institute of Internal Medicine, University of Siena, Italy. figura unisi.it

Lansoprazole is a gastric parietal cell proton pump inhibitor that is also active against Helicobacter pylori in vitro. We aimed to investigate further the mechanism of its antimicrobial effect. The antimicrobial activity of lansoprazole and of its sulfenamide, a rearrangement product occurring spontaneously in acid environments, was studied by determining the MICs and MBCs for 11 cytotoxic and eight non-cytotoxic H. pylori strains and by measuring the rapidity of bacterial killing. The MIC90 and MBC90 were 2.5 mg/L and 10 mg/L, respectively, both for lansoprazole and for its sulfenamide. Cytotoxic strains were as susceptible as non-cytotoxic strains. The sulfenamide exhibited faster bactericidal activity. Lansoprazole did not inhibit the toxin-induced vacuolization of HeLa cells by a cytotoxic strain, hence its anti-H. pylori activity does not depend on inhibition of a v-ATPase-mediated, toxin-induced activity. Sulfenamide formation is likely to occur in vivo in the gastric environment, thus enhancing the bactericidal activity of the drug. Lansoprazole is likely to be useful, in association with antibiotics, in the treatment of H. pylori infection regardless of the cytotoxicity of the infecting strain.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9184356&dopt=Abstract lansoprazole Prevacid



Prevacid
High-performance thin-layer chromatographic method for the detection and determination of lansoprazole in human plasma and its use in pharmacokinetic studies.

Pandya KK, Mody VD, Satia MC, Modi IA, Modi RI, Chakravarthy BK, Gandhi TP.

Department of Phytochemistry, R & D, Cadila Pharmaceuticals Ltd., Ahmedabad, India.

A rapid and sensitive high-performance thin-layer chromatography (HPTLC) method has been developed for the measurement of lansoprazole in human plasma and its use for pharmacokinetic study has been evaluated. Detection and quantitation were performed without using an internal standard. A single stage extraction procedure was followed for extracting lansoprazole from plasma and a known amount of the extract was spotted on precoated silica gel 60 F254 plates using a Camag Linomat IV autosampler. Lansoprazole was quantified using a Camag TLC Scanner 3. The recovery study of authentic analytes added to plasma at 0.05 to 0.25 microg/ml was 95.37+/-2.15% and the lowest amount of lansoprazole that could be detected was 20 ng/ml plasma. The method provides a direct estimate of the amount of lansoprazole present in plasma. The method was used for the determination of plasma levels as well as pharmacokinetic parameters of lansoprazole after oral administration of two marketed preparations to healthy volunteers.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9200535&dopt=Abstract lansoprazole Prevacid



Prevacid
Different contribution of CYP2C19 in the in vitro metabolism of three proton pump inhibitors.

Kita T, Sakaeda T, Baba T, Aoyama N, Kakumoto M, Kurimoto Y, Kawahara Y, Okamura N, Kirita S, Kasuga M, Okumura K.

Department of Hospital Pharmacy, School of Medicine, Kobe University, Chuo-ku, Japan.

A series of clinical studies on the cytochrome P450 2C19 (CYP2C19) genotype and the pharmacokinetics and pharmacodynamics of three proton pump inhibitors (PPIs), omeprazole, lansoprazole and rabeprazole, have been conducted to establish the individualized pharmacotherapy based on the CYP2C19 genotyping, and in the present study, the CYP2C19 genotype-dependency was more pronounced for omeprazole than the other two. Herein, to validate further the difference among 3 PPIs in CYP2C19 genotype-dependency on the phenotype, a comparative in vitro study was conducted using the human liver microsomes and newly developed anti-human CYP antibodies. The residual concentrations of omeprazole and lansoprazole in 5 lots of human liver microsomes were dependent on the CYP2C19 activities, however, for rabeprazole, there was no correlation. The hydroxylation of omeprazole was more inhibited by anti-CYP2C19 antibody than lansoprazole, whereas anti-CYP3A4 antibody showed similar inhibition. In conclusion, the relative contribution of CYP2C19 on total metabolism of 3 PPIs elucidated herein coincided with the CYP2C19 genotype-dependent pharmacokinetics.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12612455&dopt=Abstract lansoprazole Prevacid