Prevacid
[Investigation of the effects of eflux pump inhibitors on ciprofloxacin MIC values of high level fluoroquinolone resistant Escherichia coli clinical isolates]

[Article in Turkish]

Coban AY, Birinci A, Ekinci B, Durupinar B.

Ondokuz Mayis Universitesi Tip Fakultesi, Mikrobiyoloji ve Klinik Mikrobiyoloji Anabilim Dali, Samsun.

In this study, effects of eflux pump inhibitors, phe-arg-beta-naphthylamide (MC-207,110), verapamil, omeprazole and lansoprazole, on ciprofloxacin minimal inhibitory concentrations (MIC) against Escherichia coli clinical isolates with high level fluoroquinolone (FQ) resistance, were evaluated. Fourteen FQ resistant clinical isolates of E. coli isolated from urine samples and identified by BD BBL CRYSTAL Identification Systems Enteric/Nonfermenter ID kit (Becton Dickinson and Company Sparks, USA) were tested. In order to investigate the effects of inhibitory agents, MIC values were determined by broth microdilution method in the absence or presence of 20 microg/ml MC-207,110, verapamil, omeprazole and lansoprazole. All 14 clinical isolates were resistant to ciprofloxacin (MIC range; 16-512 microg/ml). No difference was observed on ciprofloxacin MIC values in the presence of 20 microg/ml omeprazole, whereas MIC values were decreased 2 folds in 2 isolates in the presence of verapamil and lansoprazole, 2 folds in 6 isolates and 4 folds in 2 isolates in the presence of MC-207,110. In conclusion, we observed that there were no effects of the compounds used in our study, on ciprofloxacin resistance of E. coli clinical isolates.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15293898&dopt=Abstract lansoprazole Prevacid



Prevacid
Pharmacokinetics of lansoprazole in Chinese healthy subjects in relation to CYP2C19 genotypes.

Hu YR, Qiao HL, Kan QC.

Department of Clinical Pharmacology, School of Medicine, Zhengzhou University, Zhengzhou 450052, China.

AIM: To study the kinetic characteristics of lansoprazole in healthy Chinese subjects in relation to CYP2C19 genotype status for the individualized dose regimen of lansoprazole. METHODS: Nine homozygous extensive metabolizers (homo EMs) and 9 poor metabolizers (PMs) were recruited for the study from a total of 70 healthy Chinese volunteers, whose CYP2C19 genotype status was determined by the PCR-RFLP techniques. After a single oral dose of 30 mg lansoprazole capsule, plasma concentrations of lansoprazole were determined with HPLC method. RESULTS: In Chinese subjects, the allele frequencies of the CYP2C19m1 and CYP2C19m2 mutation were 0.35 and 0.07, respectively. The concentration-time curves in the two groups were best fitted to a one-compartment model. In the homo EMs and the PMs groups, the main kinetic parameters were as follows: Tmax (2.44+/-0.85) and (2.33+/-0.94) h, Cmax(1.10+/-0.34) and (1.73+/-0.56) mg/L, Cl/F (16.55+/-0.38) and (3.58+/-1) L/h, T1/2ke (1.96+/-0.51) and (4.21+/-0.53) h, AUC were (3.23+/-0.08) and (11.05+/-0.23) mg.L(-1). A significant difference in AUC, T1/2ke, Cl/F, Cmax values existed between the two groups (P<0.01). CONCLUSION: CYP2C19 genotype is the major factor to influence the interindividual kinetic variability of lansoprazole. Individualized dose regimen of lansoprazole, based on identification of genotype, can be of great benefit for the reasonable use of this drug.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15301728&dopt=Abstract lansoprazole Prevacid



Prevacid
Lansoprazole ameliorates intestinal mucosal damage induced by ischemia-reperfusion in rats.

Ichikawa H, Yoshida N, Takagi T, Tomatsuri N, Katada K, Isozaki Y, Uchiyama K, Naito Y, Okanoue T, Yoshikawa T.

Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.

AIM: To investigate the protective effect of lansoprazole on ischemia and reperfusion (I/R)-induced rat intestinal mucosal injury in vivo. METHODS: Intestinal damage was induced by clamping both the superior mesenteric artery and the celiac trunk for 30 min followed by reperfusion in male Sprague-Dawley rats. Lansoprazole was given to rats intraperitoneally 1 h before vascular clamping. RESULTS: Both the intraluminal hemoglobin and protein levels, as indices of mucosal damage, significantly increased in I/R-groups comparison with those of sham-operation groups. These increases in intraluminal hemoglobin and protein levels were significantly inhibited by the treatment with lansoprazole at a dose of 1 mg/kg. Small intestine exposed to I/R resulted in mucosal inflammation that was characterized by significant increases in thiobarbituric acid-reactive substances (TBARS), tissue-associated myeloperoxidase activity (MPO), and mucosal content of rat cytokine-induced neutrophil chemoattractant-1 (CINC-1). These increases in TBARS, MPO activities and CINC-1 content in the intestinal mucosa after I/R were all inhibited by pretreatment with lansoprazole at a dose of 1 mg/kg. Furthermore, the CINC-1 mRNA expression was increased during intestinal I/R, and this increase in mRNA expression was inhibited by treatment with lansoprazole. CONCLUSION: Lansoprazole inhibits lipid peroxidation and reduces development of intestinal mucosal inflammation induced by I/R in rats, suggesting that lansoprazole may have a therapeutic potential for I/R injury.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15334676&dopt=Abstract lansoprazole Prevacid



Prevacid
Determination of lansoprazole in pharmaceutical capsules by flow injection analysis using UV-detection.

Yeniceli D, Dogrukol-Ak D, Tuncel M.

Department of Analytical Chemistry, Faculty of Pharmacy, University of Anadolu, 26470 Eskisehir, Turkey.

The direct determination of lansoprazole by using a flow injection analysis (FIA) with UV-detection and its application to the pharmaceutical capsules is described, in this study. The best carrier solvent was found to be 0.01 M NaOH and it was determined at optimum conditions such as flow rate of 1 ml min(-1) and wavelength of 292 nm. Examining the repeatability of the method that was found to be 1.72% for intra-day and 2.13% for inter-day precision using the 8.01 x 10(-6) M lansoprazole concentration has validated the method. The linear range of the method was 5.4 x 10(-6) to 5.4 x 10(-5) M. The limit of detection and quantification was found to be 5.8 x 10(-7) and 1.7 x 10(-6) M, respectively. The proposed method was applied to the pharmaceutical capsules and very good results obtained. Thus, the FIA method for the quantification of lansoprazole can be proposed as a cheap, rapid, easy, accurate, and precise method for the routine determination in pharmaceutical preparations.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15351058&dopt=Abstract lansoprazole Prevacid



Prevacid
CYP2C19 polymorphism is a major predictor of treatment failure in white patients by use of lansoprazole-based quadruple therapy for eradication of Helicobacter pylori.

Schwab M, Schaeffeler E, Klotz U, Treiber G.

Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Auerbachstrasse 112, D-70376 Stuttgart, Germany. matthias.schwab ikp.stuttgart.de

OBJECTIVE: Proton pump inhibitors, metabolized by the polymorphic enzyme cytochrome P450 (CYP) 2C19, are essential drugs for Helicobacter pylori eradication. It was reported that patients with CYP2C19 wild type in Asia had lower eradication rates. This study tests the hypothesis that CYP2C19 wild type ( wt/wt ) in white patients is also associated with a higher probability of treatment failure. METHODS: This was a cohort study involving 131 H pylori -positive white (German) patients treated by quadruple therapy including lansoprazole (30 mg twice daily for 5 days). Eradication success, as well as lansoprazole trough steady-state serum concentrations, was determined according to different CYP2C19 genotypes. RESULTS: We found 3 homozygous variant patients (2.3%) ( mt/mt, CYP2C19*2/*2 ), 42 heterozygous patients (32.1%) ( wt/mt, CYP2C19*1/*2 ), and 86 wild-type individuals (65.6%). Significant differences in eradication success could be found between wt/wt patients (80.2%) versus combined mt/mt (100%) and wt/mt patients (97.8%) ( P <.01; odds ratio, 10.8 [confidence interval, 1.4-84]), which were associated with corresponding changes in the serum levels of lansoprazole (median, 753 ng/mL for mt/mt, 59 ng/mL for wt/mt, and 21 ng/mL for wt/wt; P <.001). Apart from antibiotic resistance, CYP2C19 polymorphism was the most important influencing factor for eradication success on multivariate analysis ( P <.0001). CONCLUSION: Eradication rates of H pylori highly depend on CYP2C19 in white patients if standard doses of lansoprazole (30 mg twice daily) are administered within a quadruple regimen. Because wt/wt individuals have lower eradication rates and lower serum concentrations of lansoprazole, these patients might benefit from a higher proton pump inhibitor dosage.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15371981&dopt=Abstract lansoprazole Prevacid