Patient adherence is vital for Helicobacter pylori eradication. Simplifying therapy dosing schedules may promote patient adherence, enhance treatment success rates, and help mitigate the development of antibiotic resistance. We aimed to assess plasma and intragastric rifabutin, amoxicillin, and omeprazole concentrations comparing two dosing schedules of RHB-105 (every 8 h and a more flexible three-times daily schedule, at 8 a.m., 12 p.m., and 6 p.m.) using a validated physiologically based pharmacokinetic (PBPK) model. Leveraging in vitro and in vivo information on the pharmacokinetics of the three components of RHB-105, we developed mechanistic absorption PBPK models to predict plasma and intragastric concentration-time profiles for each component. There were only negligible differences in the area under the concentration-time curves (AUC) for plasma and the intragastric compartment, and maximal concentration (Cmax) with only up to a 1.1-fold difference for rifabutin, amoxicillin, and omeprazole between dosing schedules. Overlapping 90% confidence intervals for both AUC and Cmax support that overall exposures are comparable regardless of dosing every 8 h or three-times daily for all three drugs. Drug exposure was highly similar for rifabutin, amoxicillin, and omeprazole with each dosing schedule. Novel mechanistic absorption PBPK modeling supports the approval and use of the more flexible dosing schedule for RHB-105, simplifying patient experience and potentially increasing adherence.

Sustained intragastric antibiotic exposure is important for Helicobacter pylori eradication, yet little is known about gastric pharmacology of commonly used H. pylori regimens. For rifabutin, differing intragastric concentrations based on dosing regimen may account for differences in reported eradication rates.

To compare intragastric rifabutin concentrations between low-dose rifabutin (50 mg three time daily; as in RHB-105) and generically dosed rifabutin 150 mg once daily, 150 mg twice daily, and 300 mg once daily using a validated Physiologically-based pharmacokinetic (PBPK) model.

We obtained plasma pharmacokinetic data from the RHB-105 clinical development programs and used it to develop and validate a whole-body PBPK model using PK-SIM software. We modified the existing rifabutin model to include the impact of omeprazole on gastric pH and emptying time. Modelled intragastric rifabutin exposure was expressed as the time that each regimen maintained its concentration ≥MIC90 .

Rifabutin 50 mg three times daily achieved significantly longer times with intragastric concentration above MIC90 (22.3 ± 1.1 h) than 150 mg once daily (8.3 ± 1.7 h), 150 mg twice daily (16.3 ± 2.3 h), or 300 mg once daily (8.5 ± 1.9 h) while providing the lowest mean maximal plasma concentration and mean area under the plasma concentration-time curve of all regimens studied.

PBPK modelling showed rifabutin 50 mg three times daily had higher intragastric exposure times than 150 mg once daily or twice daily, or 300 mg once daily. This low-dose rifabutin regimen provides the highest potential for H. pylori eradication while minimising systemic rifabutin exposure.

The objective of this study was to compare the prevalence of Helicobacter pylori (HP) seropositivity in patients undergoing bariatric surgery with that of the general population.

H. pylori serologies, tested by ELISA, were collected on 240 morbidly obese patients seen at the Cleveland Clinic Florida and on 2444 randomly selected patients seen at the Cleveland Clinic Health System from 2003-2005.

H. pylori prevalence was 61.3% in the bariatric surgery group versus 48.2% in the general population control group (p < 0.001). Bariatric patients had a 1.7-fold increased likelihood of having HP when compared with controls (95% CI = 1.3-2.2). Age over 35 years was an independent risk factor for HP seropositivity (p < 0.01) in both the bariatric and control groups. There was no association found between body mass index and seropositivity within the bariatric group. There was no significant association between seropositivity and gender (p = 0.776). However, there was a significant association between seropositivity and race (p < 0.01). African-Americans had four times more (OR = 4.05) probability of having HP seropositivity than Caucasians (p < 0.01). Hispanics had almost three times (OR = 2.6) more probability of having HP seropositivity than Caucasians (p < 0.01).

The prevalence of HP seropositivity among bariatric patients is significantly higher than the general population control group.

To evaluate the gastric emptying inhibitory effects of sugar and levodopa on H pylori eradication period.

A total of 139 consecutive patients were randomized into 6 groups. The participants with peptic ulcer disease or non-ulcer dyspepsia non-responding to other medications who were also H pylori-positive patients either with positive rapid urease test (RUT) or positive histology were included. All groups were pretreated with omeprazole for 2 d and then treated with quadruple therapy regimen (omeprazole, bismuth, tetracycline and metronidazole); all drugs were given twice daily. Groups 1 and 2 were treated for 3 d, groups 3, 4 and 5 for 7 d, and group 6 for 14 d. Groups 1 to 4 received sugar in the form of 10% sucrose syrup. Levodopa was prescribed for groups 1 and 3. Patients in groups 2 and 4 were given placebo for levodopa and groups 5 and 6 received placebos for both sugar and levodopa. Upper endoscopy and biopsies were carried out before treatment and two months after treatment. Eradication of H pylori was assessed by RUT and histology 8 wk later.

Thirty patients were excluded. Per-protocol analysis showed successful eradication in 53% in group 1, 56% in group 2, 58% in group 3, 33.3% in group 4, 28% in group 5, and 53% in group 6. Eradication rate, patient compliance and satisfaction were not significantly different between the groups.

It seems that adding sugar or levodopa or both to anti H pylori eradication regimens may lead to shorter duration of treatment.

The main objective of the study was to develop a stomach-specific drug delivery system to increase the efficacy of tetracycline against Helicobacter pylori. Chitosan microspheres were prepared by ionic cross-linking and precipitation with sodium sulfate. Two different methods were used for drug loading. In method I, tetracycline was mixed with chitosan solution before the simultaneous cross-linking and precipitation. In method II, the drug was incubated with pre-formed microspheres for 48 h. The cumulative amount of tetracycline that was released from chitosan microspheres and the stability of the drug was examined in different pH medium at 37 degrees C. Microspheres with a spherical shape and an average diameter of 2.0-3.0 microm were formed. When the drug was added to the polymer solution before cross-linking and precipitation only 8% (w/w) was optimally incorporated in the final microsphere formulation. When the drug was incubated with the pre-formed microspheres, on the other hand, a maximum of 69% (w/w) could be loaded. Thirty percent of tetracycline either in solution or when released from microspheres was found to degrade at pH 1.2 in 12 h. The preliminary results from this study suggest that chitosan microspheres can be used to incorporate antibiotic drugs and may be effective when administered locally in the stomach against H. pylori.