Prevacid
The long-lasting effect of TU-199, a novel H+, K(+)-ATPase inhibitor, on gastric acid secretion in dogs.

Uchiyama K, Wakatsuki D, Kakinoki B, Takeuchi Y, Araki T, Morinaka Y.

Medicinal Research Group II, Kazusa Research Laboratories, Tokyo Tanabe Company Limited, Chiba, Japan. k-uchiy kazusa.tokyo-tanabe.co.jp

We have used Heidenhain-pouch dogs to investigate the effects of (+/-)-5-methoxy-2- inverted question mark[(4-methoxy-3,5-dimethylpyrid-2-yl)methyl]sulph inyl inverted question mark-1H-imidazo[4,5-b]pyridine (TU-199), an imidazopyridine derivative, on gastric acid secretion stimulated by histamine, carbachol and tetragastrin. We have also investigated the duration of the antisecretory effect of TU-199 using a measurement of intragastric pH for 24 h in gastric fistula dogs whose gastric acid secretion was stimulated by histamine. Single oral administration of TU-199 (0.1, 0.2 and 0.4mgkg(-1)) dose-dependently suppressed gastric acid secretion stimulated by histamine infusion. Oral treatment with TU-199 (0.2, 0.4 and 0.8 mg kg(-1)) also dose-dependently inhibited acid secretion induced by carbachol and tetragastrin. The inhibitory effect of TU-199 on stimulated gastric acid secretion was more potent than that of omeprazole, a well-known H+,K(+)-ATPase inhibitor in dogs. Repeated oral treatment with TU-199 at a dose of 0.2 mg kg(-1) once a day for seven days markedly suppressed histamine-stimulated gastric acid secretion in dogs. This inhibitory effect of TU-199 reached a maximum level after three or four doses and was more pronounced than that of omeprazole or lansoprazole. In gastric fistula dogs, the duration of intragastric pH-elevation by administration of TU-199 (0.3 mg kg(-1)) was much longer than that of omeprazole (0.6mgkg(-1)) or lansoprazole (0.9mgkg(-1)). The IC50 values (doses resulting in 50% inhibition) of TU-199, omeprazole and lansoprazole with regard to H+,K(+)-ATPase activity in dog gastric mucosal microsomes were 8.6, 8.8 and 9.9 microM, respectively. These results indicate that TU-199 inhibits gastric acid secretion via suppression of a H+,K(+)-ATPase activity. Our findings also suggest that TU-199 might have potent and long-lasting effects on gastric acid secretion.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10385219&dopt=Abstract lansoprazole Prevacid



Prevacid
The Effects of Lansoprazole on the Disposition of Antipyrine and Indocyanine Green in Normal Human Subjects.

St Peter JV, Awni WM, Granneman GR, Karol MD.

The Drug Evaluation Unit, Hennepin County Medical Center, Minneapolis, MN, USA and College of Pharmacy, University of Minnesota, Minneapolis, MN, USA.

This study was designed to evaluate the potential effects of acute and chronic daily oral doses of lansoprazole (60 mg) on the disposition of antipyrine, an almost completely metabolized low hepatic extraction compound, and indocyanine green, a hepatically secreted compound with high extraction ratio. The study utilized a randomized, placebo-controlled, double-blind, two-period crossover design. Sixteen of 18 subjects completed all phases of the study. Both antipyrine (10 mg kg(minus sign1)) and indocyanine green (0.5 mg kg(minus sign1)) were administered as single intravenous bolus doses on Days 1 and 7 of lansoprazole or placebo dosing. Acute exposure to lansoprazole had no statistically significant effects on the plasma pharmacokinetics of indocyanine green or antipyrine. After the seventh dose, there was a small but statistically significant reductions in indocyanine green total body clearance (CL), and elimination rate constant of 10.6% and 8%, respectively. Additionally, a small statistically significant reduction (8.6%) in antipyrine volume of distribution was detected. No other plasma antipyrine pharmacokinetic parameters were changed with concomitant lansoprazole administration. About a 12% increase in the recovery of one of the major antipyrine urine metabolites (NORA) was detected. Overall, this study demonstrates little or no effect of lansoprazole on the pharmacokinetics of antipyrine and indocyanine green.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11854827&dopt=Abstract lansoprazole Prevacid



Prevacid
Lansoprazole pharmacokinetics differ in patients with oesophagitis compared to healthy volunteers.

Barclay ML, Begg EJ, Robson RA, Peters WA, Ketelbey JW.

Department of Clinical Pharmacology, Christchurch Hospital, Christchurch, New Zealand.

AIM: To compare the pharmacokinetics of lansoprazole in patients with reflux oesophagitis and in healthy volunteers, after a single dose and at steady-state. PATIENTS AND METHODS: A 30 mg dose of lansoprazole was administered orally daily for 7 days in eight healthy male volunteers aged 21-24 years, and in 16 patients aged 29-65 years with grade 2 or 3 reflux oesophagitis. The pharmacokinetics were assessed over the 24 h dose interval following the first dose and again after the 7th dose. RESULTS: Within both the patient and volunteers groups, there were no significant differences between day 1 and day 7 in any of the pharmacokinetic parameters including maximum concentration (Cmax), area under the concentration-time curve (AUC), and terminal half-life of elimination (t(1/2)). However, on both days 1 and 7, values were significantly higher in the patients than in the healthy volunteers. On day 7, Cmax was 1343 ng/mL in patients compared with 765 ng/mL in healthy volunteers, AUC was 3458 ng.h/mL vs. 1350 ng.h/mL and t(1/2) was 1.62 h vs. 0.90 h. CONCLUSION: The differences in results for the pharmacokinetics reflect reduced lansoprazole clearance in the patient group. Other research has not found a difference in pharmacokinetics when comparing healthy volunteers with patients with acid-related disorders. The difference in lansoprazole clearance in this study may be related to a variety of factors that are different in patients compared with young normal volunteers, such as age, gender, other drugs, and reduced general well-being.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10468704&dopt=Abstract lansoprazole Prevacid



Prevacid
Effects of acid suppression and bismuth medications on the performance of diagnostic tests for Helicobacter pylori infection.

Bravo LE, Realpe JL, Campo C, Mera R, Correa P.

Department of Pathology, Universidad del Valle, Cali, Colombia.

OBJECTIVE: This study was designed to investigate whether acid suppression and bismuth medications interfere with the performance of diagnostic tests for Helicobacter pylori (H. pylori) infection. METHODS: Sixty patients with previous diagnoses of atrophic gastritis and H. pylori infection made in gastric biopsies taken at Hospital Departmental, Pasto, Colombia, were enrolled in the study. 13C breath urea test (UBT) and stool antigen test (HpSA) were performed simultaneously. Two baseline tests were performed: one 7 days before and another the day before starting medications. A total of 20 patients received for 2 wk one of the following treatments: a) ranitidine; b) lansoprazole; or c) bismuth subsalicylate. The tests were repeated while the patients were on the prescribed medication on days 7 and 14 and then 2 wk after finishing the medication. RESULTS AND CONCLUSIONS: Utilizing standard cut-off values for the tests, our results indicate that in the case of the 13C UBT test, ranitidine does not interfere with the results, whereas lansoprazole and bismuth may be expected to yield a significant proportion of false negative results (30-40% for lansoprazole and 45-55% for bismuth). In the case of the HpSA test, ranitidine does not interfere, whereas lansoprazole and bismuth may be expected to yield a nonsignificant proportion of false negative results (15-25% for lansoprazole and 10-15% for bismuth). Absolute values for both tests may be used to study the effects of the pharmacological agents on the characteristics of the infection.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10483995&dopt=Abstract lansoprazole Prevacid



Prevacid
Effect of various salts on the stability of lansoprazole, omeprazole, and pantoprazole as determined by high-performance liquid chromatography.

Ekpe A, Jacobsen T.

Bayer Corporation, Morristown, NJ 07962-1910, USA. Anthony.Ekpe.B Bayer.com

A fast and reproducible reverse-phase high-performance liquid chromatography (HPLC) assay method has been developed for the simultaneous quantitation of omeprazole, lansoprazole, and pantoprazole. The three compounds were monitored at 280 nm using Zorbax Eclipse XDB C8 (5 microns, 150 cm x 4.6 mm i.d.) and a mobile phase consisting of 700:300 phosphate buffer:acetonitrile with the pH adjusted to 7.0 with phosphoric acid. The method was used to study the effect of pH and various salts on the stability of the three compounds. The pH rate profile curve showed that pantoprazole was the most stable compound and lansoprazole the least stable. The stabilities of the compounds in salt solutions were found to be in the following order: phosphate buffer < trisodium citrate < citrate buffer < or = acetate buffer < citric acid < or = monosodium citrate < or = calcium carbonate < sodium bicarbonate < sodium chloride < water. The rate of degradation had a direct relationship with the H+ and salt concentration.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10518247&dopt=Abstract lansoprazole Prevacid