Prevacid
Formulation study for lansoprazole fast-disintegrating tablet. III. Design of rapidly disintegrating tablets.

Shimizu T, Sugaya M, Nakano Y, Izutsu D, Mizukami Y, Okochi K, Tabata T, Hamaguchi N, Igari Y.

Pharmaceutical Development Laboratories, Pharmaceutical Production Division, Takeda Chemical Industries, Ltd., Osaka, Japan. Shimizu_Toshihiro takeda.co.jp

Lansoprazole fast-disintegrating tablets (LFDT) are a patient-friendly formulation that rapidly disintegrates in the mouth. LFDT consist of enteric-coated microgranules (mean particle size, approximately 300 microm) and inactive granules. In the design of the inactive granules, mannitol was used as a basic excipient. Microcrystalline cellulose, low-substituted hydroxypropyl cellulose (L-HPC), and crospovidone were used as binders and disintegrants. A new grade of L-HPC (L-HPC-33), with a hydroxypropoxy group content of 5.0-6.9%, was developed and it has no rough texture due to a decrease in water absorption. It was clarified that L-HPC-33 could be useful as a binder and disintegrant in rapidly disintegrating tablets. LFDT contain enteric-coated microgranules in tablet form. The enteric-coated microgranule content in LFDT affect qualities such as tensile strength, disintegration time in the mouth, and dissolution behavior in the acid stage and in the buffer stage of LFDT. The 47.4% content of the enteric-coated microgranules was selected to give sufficient tensile strength (not less than 30 N/cm(2)), rapid disintegration time in the mouth (not more than 30 s), and dissolution behavior in the acid stage and buffer stage similar to current lansoprazole capsules. Compression force affected the tensile strength and the disintegration time in the mouth, but did not affect the dissolution behavior in the acid and buffer stages.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14519914&dopt=Abstract lansoprazole Prevacid



Prevacid
Lansoprazole increases testosterone metabolism and clearance in male Sprague-Dawley rats: implications for Leydig cell carcinogenesis.

Coulson M, Gibson GG, Plant N, Hammond T, Graham M.

Molecular Toxicology Group, School of Biomedical & Life Sciences, University of Surrey, Guildford GU2 7XH, UK.

Leydig cell tumours (LCTs) are frequently observed during rodent carcinogenicity studies, however, the significance of this effect to humans remains a matter of debate. Many chemicals that produce LCTs also induce hepatic cytochromes P450 (CYPs), but it is unknown whether these two phenomena are causally related. Our aim was to investigate the existence of a liver-testis axis wherein microsomal enzyme inducers enhance testosterone metabolic clearance, resulting in a drop in circulating hormone levels and a consequent hypertrophic response from the hypothalamic-pituitary-testis axis. Lansoprazole was selected as the model compound as it induces hepatic CYPs and produces LCTs in rats. Male Sprague-Dawley rats were dosed with lansoprazole (150 mg/kg/day) or vehicle for 14 days. Lansoprazole treatment produced effects on the liver consistent with an enhanced metabolic capacity, including significant increases in relative liver weights, total microsomal CYP content, individual CYP protein levels, and enhanced CYP-dependent testosterone metabolism in vitro. Following intravenous administration of [14C]testosterone, lansoprazole-treated rats exhibited a significantly smaller area under the curve and significantly higher plasma clearance. Significant reductions in plasma and testicular testosterone levels were observed, confirming the ability of this compound to perturb androgen homeostasis. No significant changes in plasma LH, FSH, or prolactin levels were detected under our experimental conditions. Lansoprazole treatment exerted no marked effects on testicular testosterone metabolism. In summary, lansoprazole treatment induced hepatic CYP-dependent testosterone metabolism in vitro and enhanced plasma clearance of radiolabelled testosterone in vivo. These effects may contribute to depletion of circulating testosterone levels and hence play a role in the mode of LCT induction in lansoprazole-treated rats.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14550749&dopt=Abstract lansoprazole Prevacid



Prevacid
Influence of anti-ulcer drugs used in Japan on the result of (13)C-urea breath test for the diagnosis of Helicobacter pylori infection.

Murakami K, Sato R, Okimoto T, Watanabe K, Nasu M, Fujioka T, Kodama M, Kagawa J.

Second Department of Internal Medicine, Oita Medical University, 1-1 Hasama, 879-5593 Oita, Japan.

BACKGROUND: The (13)C-urea breath test (UBT) is a simple breath test for the diagnosis of Helicobacter pylori infection, but several factors have been reported to affect the results of this test. In this study, the effects of the antiulcer drugs used in Japan on the results of UBT were determined. METHODS: The subjects of the study were 64 adult volunteers who tested positive for H. pylori infection by the serum antibody method. Eight classes of anti-ulcer drugs used in Japan were administered at their usual doses to these subjects: lansoprazole, a proton pump inhibitor (PPI); nizatidine, an H(2)-receptor antagonist (H(2)RA); and polaprezinc, ecabet sodium, rebamipide, teprenone, cetraxate hydrochloride, and sucralfate, all mucoprotective agents. The study drugs were randomized for administration to the subjects, and each of the drugs was administered for 14 consecutive days. The UBT was performed on days 0, 14, and 21. RESULTS: The mean Delta(13)C per thousand in the lansoprazole group was significantly decreased on day 14, to below 10 per thousand, in 4 of 16 subjects, and in 1 of the 4 subjects, the test result was negative, with the Delta(13)C per thousand falling to 1.7 per thousand. The value returned to baseline 1 week after the discontinuation of lansoprazole. The other drugs administered had no significant effect on the result of the UBT, except that the mean Delta(13)C per thousand showed a tendency to decrease after the administration of ecabet sodium and rebamipide. CONCLUSIONS: Administration of a PPI may produce a false-negative UBT result, while other anti-ulcer drugs, for the most part, have little effect on the result of the UBT when used alone. The (13)C-urea breath test (UBT) is a simple test for the diagnosis of Helicobacter pylori infection, but several factors have been reported to affect the results of this test. In this study, the effects of the anti-ulcer drugs used in Japan on the results of the UBT were determined.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14614600&dopt=Abstract lansoprazole Prevacid



Prevacid
Symptomatic and endoscopic outcome of heartburn 3-4.5 years after starting lansoprazole therapy: a prospective study of 142 patients.

Abu Farsakh N.

University Health Center, Jordan University of Science and Technology, Irbed, Jordan.

BACKGROUND: Heartburn is a common symptom with great impact on quality of life and on the economy. An approach that helps to alleviate patients' symptoms, decrease the burden on the economy, and improve longterm outcome is needed. Step-down therapy, starting with the proton pump inhibitor lansoprazole, seems to achieve these goals. METHODS: All patients who were referred to the gastroenterology clinic at the University Health Center to evaluate their heartburn and who met the inclusion criteria were included in the present study. Symptomatic and endoscopic evaluations were carried out and then they were started on the proton pump inhibitor lansoprazole to achieve symptomatic control. Step-down therapy was carried out for these patients, provided their symptoms remained controlled. At the end of the study symptomatic and endoscopic outcomes were evaluated. RESULTS: Heartburn was controlled on lansoprazole 30 mg/per day in 76.1% of patients, and 18.3% required double this dose. Initial endoscopy showed normal findings in 38.7%, while 61.3% showed various grades of esophagitis including 1.4% with Barrett's epithelium. Of 119 patients who completed the study, 17 were non-compliant to therapy, 52 were controlled on minimal therapy, 42 required lansoprazole to be kept symptom-free, and 8 patients had surgery. Endoscopic esophagitis was healed or attenuated in all compliant patients. No new cases of Barrett's appeared during follow up. CONCLUSIONS: Most of the patients with heartburn can be controlled on proton pump inhibitors, with improvement in the grade of endoscopic esophagitis. Half of these patients can be kept on minimal therapy after a period of 3-4.5 years with maintenance of improvement, while the remainder still need proton pump inhibitors for control.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14673720&dopt=Abstract lansoprazole Prevacid



Prevacid
Interaction of omeprazole, lansoprazole and pantoprazole with P-glycoprotein.

Pauli-Magnus C, Rekersbrink S, Klotz U, Fromm MF.

Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany. christiane.pauli-magnus ikp-stuttgart.de

Proton pump inhibitors are a class of drugs which are widely prescribed for acid-related diseases. They are primarily metabolized by CYP2C19 and CYP3A4. It is unknown so far whether proton pump inhibitors are also substrates of the ATP-dependent efflux transporter P-glycoprotein. Moreover, it is not established whether proton pump inhibitors are also inhibitors of P-glycoprotein function. The aim of our study was therefore to characterize omeprazole, lansoprazole and pantoprazole as P-glycoprotein substrates and inhibitors. Polarized transport of these compounds was assessed in P-glycoprotein-expressing Caco-2 and L-MDR1 cells. Inhibition of P-glycoprotein-mediated transport was determined using the cyclosporine analogue PSC-833 (valspodar) as P-glycoprotein inhibitor. Inhibition of efflux transport by omeprazole, lansoprazole and pantoprazole was assessed using digoxin as P-glycoprotein substrate. At concentrations of 5 microM, basal-to-apical transport of omeprazole, lansoprazole and pantoprazole was greater than apical-to-basal transport in Caco-2 and L-MDRI cells. Addition of PSC-833 (1 microM) showed a clear effect only for lansoprazole, suggesting that other transporters contribute to omeprazole and pantoprazole cellular translocation. Furthermore, all of the tested compounds inhibited digoxin transport with IC50 values of 17.7, 17.9 and 62.8 microM for omeprazole, pantoprazole and lansoprazole, respectively. In summary, our data provide evidence that proton pump inhibitors are substrates and inhibitors of P-glycoprotein. These findings might explain some of the drug interactions with proton pump inhibitors observed in vivo.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11770010&dopt=Abstract lansoprazole Prevacid