Prevacid
Spectrophotometric methods for the determination of lansoprazole and pantoprazole sodium sesquihydrate.

Moustafa AA.

Department of Analytical Chemistry, Faculty of Pharmacy, Cairo University, Egypt.

Spectrophotometric procedures for determination of two irreversible proton pump inhibitors, lansoprazole (I) and pantoprazole sodium sesquihydrate (II) are presented. Two methods were based on charge transfer complexation reaction of these drugs, where they act as n-donors, with either pi acceptor 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and with sigma acceptor as iodine. A third method was also investigated depending on ternary complex formation with eosin and copper (II). The colored products were quantified spectrophotometrically using absorption bands at 457 nm for DDQ (method A) at 293 and 359 nm for iodine (method B) and at 549 nm using ternary complex formation (method C), for both drugs. The molar combining ratio and the optimum assay conditions were studied. These methods determined the lansoprazole in concentration ranges from 10 to 90, 1.48 to 6.65 and 3.69 to 16.61 microg ml(-1) with mean percentage recovery 99.63% for DDQ, 99.71%, 99.18% for iodine and 99.76% for ternary complex and with relative standard deviation 0.11, 0.24, 0.13 and 0.36%, respectively. For pantoprazole, the concentration ranges were 10-60, 17.7-141.6 and 4.3-25.9 microg ml(-1) with mean percentage recovery 99.51, 98.97, 99.84 and 99.46% and relative standard deviation 0.53, 1.21, 0.65, 0.81% for the three mentioned methods, respectively. Investigation of the formed complexes was made with respect to its composition, molar ratio of the reaction, association constant K(C)AD, molar absorptivity epsilon(lambda)AD and free energy change deltaG for methods (A) and (B). The proposed methods have been applied successfully to the analysis of the cited drugs either in pure form or in pharmaceutical formulations, with good accuracy and precision, compared statistically with those given by the reported methods. They are recommended for quality control and routine analysis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10727122&dopt=Abstract lansoprazole Prevacid



Prevacid
Clinical and fiscal impact of lansoprazole intolerance in veterans with gastro-oesophageal reflux disease.

Gerson LB, Hatton BN, Ryono R, Jones W, Pulliam G, Sampliner RE, Triadafilopoulos G, Fass R.

Department of Gastroenterology, Stanford University School of Medicine and VA Palo Alto Health Care System, CA 94304, USA. Igerson leland.stanford.edu

BACKGROUND: Omeprazole was replaced by lansoprazole as the only proton pump inhibitor on the Veterans Affairs (VA) formulary in February 1997. We aimed to assess the clinical and fiscal impact of this conversion at two VA hospitals. METHODS: We identified lansoprazole intolerant patients using pharmacy databases. We reviewed medical records to obtain data regarding reasons for lansoprazole intolerance. The costs of the formulary change and the savings to the VA were calculated. RESULTS: A total of 3833 patients required long-term proton pump inhibitor therapy; 2224 (58%) were started on lansoprazole and 1479 (39%) were converted from omeprazole to lansoprazole. The remaining 130 (3.4%) patients were never converted from omeprazole to lansoprazole. Of the 3833 patients, 325 (8.5%) currently receive omeprazole therapy; of these, 195 out of 3703 (5.3%) patients are true lansoprazole failures; 172 of these 195 patients completed the study. Most (87%) of the lansoprazole intolerant patients received prior omeprazole. Discontinuation of lansoprazole was due to poor symptom control in 69% and/or side-effects (22%) including diarrhoea (10%), abdominal pain (5%), or hives (1%). The 1-year cost of managing lansoprazole failure in 195 patients was $61 690. However, the savings to the VA during the same time period, which totalled $321 360, more than offset the costs associated with the conversion. CONCLUSIONS: Lansoprazole intolerance requiring omeprazole conversion occurred in 5% of veterans on proton pump inhibitor therapy for chronic gastro-oesophageal reflux disease (GERD) symptoms and in 10% of patients with prior omeprazole success. The VA realized substantial cost savings in association with the formulary change.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10759618&dopt=Abstract lansoprazole Prevacid



Prevacid
A new mechanism for anti-inflammatory actions of proton pump inhibitors--inhibitory effects on neutrophil-endothelial cell interactions.

Yoshida N, Yoshikawa T, Tanaka Y, Fujita N, Kassai K, Naito Y, Kondo M.

First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan. nyoshida koto.kpu-m.ac.jp

BACKGROUND: Neutrophil-endothelial cell interactions mediated by adhesion molecules may be involved in gastric mucosal inflammation associated with Helicobacter pylori or nonsteroidal anti-inflammatory drugs. AIM: To investigate the effects of proton pump inhibitors and histamine-2 receptor antagonists (HRA) on neutrophil-endothelial cell adhesive interactions induced by H. pylori water extract (HPE) or interleukin-1beta (IL-1beta). METHODS: Human peripheral neutrophils and umbilical vein endothelial cells were incubated with either proton pump inhibitors (lansoprazole and omeprazole) or HRA (famotidine and ranitidine). Neutrophil surface expression of CD11b and CD18 and endothelial cell intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) were assessed by flow cytometry and an enzyme immunoassay, respectively. Neutrophil adherence was defined as the ratio of exogenous neutrophils that adhered to the endothelial monolayers. RESULTS: The expression of CD11b and CD18 on neutrophils and neutrophil-dependent adhesion to endothelial cells elicited by HPE were inhibited by lansoprazole and omeprazole at clinical relevant doses, and the expression of ICAM-1 and VCAM-1 on endothelial cells and endothelial-dependent neutrophil adherence induced by IL-1beta were also inhibited by lansoprazole and omeprazole at similar doses. Famotidine and ranitidine had no effect on neutrophil-endothelial cell interactions. CONCLUSIONS: These results indicate that proton pump inhibitors can attenuate neutrophil adherence to endothelial cells via inhibiting the expression of adhesion molecules, suggesting that proton pump inhibitors may have anti-inflammatory activity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10807407&dopt=Abstract lansoprazole Prevacid



Prevacid
Influence of age on the steady state disposition of drugs commonly used for the eradication of Helicobacter pylori.

Ammon S, Treiber G, Kees F, Klotz U.

Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology and Robert Bosch Hospital, Stuttgart, Germany. susanne.ammon ikp-stuttgart.de

BACKGROUND: The success of eradication therapy for Helicobacter pylori might be affected by the age of patients. AIM: To investigate whether disposition of drugs commonly used for H. pylori eradication is age-dependent. METHODS: Trough steady state serum levels of lansoprazole or ranitidine, amoxycillin, clarithromycin and metronidazole were monitored in 232 patients during the last dosing interval of a 5-day quadruple H. pylori eradication regimen. Detailed pharmacokinetic analysis was performed in 28 patients. RESULTS: Linear correlations between age and trough serum levels were observed with lansoprazole (r=0.25; P=0.002), ranitidine (r=0. 38; P=0.001) and clarithromycin (r=0.36; P < 0.0001). These associations were also inversely dependent of creatinine clearance for ranitidine (r=0.36; P=0.001) and clarithromycin (r=0.30; P < 0. 0001). Multiple linear regression revealed age as an important factor influencing trough serum levels of lansoprazole, clarithromycin and ranitidine. There were significant inverse relationships between creatinine clearance and area under curve of ranitidine (r=0.88; P < 0.0001) and amoxycillin (r=0.56; P=0.002). Multiple linear regression revealed serum creatinine as the most important factor influencing the area under curve of ranitidine, clarithromycin and amoxycillin. CONCLUSIONS: Age per se has little influence on pharmacokinetics of amoxycillin and ranitidine, which depend more on age-dependent decline in renal function. The influence of age, but not renal function was established for lansoprazole. Age and renal function have independent impacts on clarithromycin disposition.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10848660&dopt=Abstract lansoprazole Prevacid



Prevacid
Stability of suspension formulations of lansoprazole and omeprazole stored in amber-colored plastic oral syringes.

DiGiacinto JL, Olsen KM, Bergman KL, Hoie EB.

Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine at Peoria, USA.

OBJECTIVE: To determine the stability of lansoprazole and omeprazole suspensions at ambient and refrigerated temperatures using HPLC. DESIGN: The contents of lansoprazole and omeprazole capsules were suspended in separate flasks containing sodium bicarbonate 8.4% to concentrations of 3 and 2 mg/mL, respectively. The contents of each flask were drawn into six amber-colored oral syringes, with one-half of the syringes stored at 22 degrees C (ambient) and the other half at 4 degrees C. Lansoprazole and omeprazole concentrations were determined by a stability-indicating HPLC assay at baseline and at 4, 8, 12, and 24 hours, and on days 4, 7, 14, 21, 30, 45, and 60 after mixing. Both omeprazole and lansoprazole were considered stable if they retained > or =90% of the baseline drug concentration. RESULTS: Omeprazole was stable for up to 14 days at 22 degrees C and 45 days at 4 degrees C. Lansoprazole was stable for eight hours at 22 degrees C and for 14 days at 4 degrees C. CONCLUSIONS: When compared with ambient or refrigerated storage conditions, omeprazole was stable for a longer duration than lansoprazole. Pharmacists may use these results to guide compounding and storage of proton-pump inhibitor suspensions.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10852086&dopt=Abstract lansoprazole Prevacid