Characterization of the yehUT Two-Component Regulatory System of Salmonella enterica Serovar Typhi and Typhimurium

10.1371/journal.pone.0084567PLoS ONE812-POLN

Gastric Reacidification with Betaine HCl in Healthy Volunteers with Rabeprazole-Induced Hypochlorhydria

Previous studies have demonstrated that increased gastric pH from the use of acid-reducing agents, such as proton-pump inhibitors or H(2)-receptor antagonists, can significantly impact the absorption of weakly basic drugs that exhibit pH-dependent solubility. Clinically practical strategies to mitigate this interaction have not been developed. This pilot study evaluated the extent and time course of gastric re-acidification after a solid oral dosage form of anhydrous betaine HCl in healthy volunteers with pharmacologically-induced hypochlorhydria. Six healthy volunteers with baseline normochlorhydria (fasting gastric pH < 4) were enrolled in this single period study. Hypochlorhydria was induced via 20 mg oral rabeprazole twice daily for four days. On the fifth day, an additional 20 mg dose of oral rabeprazole was given and gastric pH was monitored continuously using the Heidelberg pH capsule. After gastric pH > 4 was confirmed for 15 minutes, 1500 mg of betaine HCl was given orally with 90 mL of water and gastric pH was continuously monitored for 2 hours. Betaine HCl significantly lowered gastric pH by 4.5 (±0.5) units from 5.2 (±0.5) to 0.6 (±0.2) (P <0.001) during the 30 minute interval after administration. The onset of effect of betaine HCl was rapid, with a mean time to pH < 3 of 6.3 (±4.3) minutes. The re-acidification period was temporary with a gastric pH < 3 and < 4 lasting 73 (±33) and 77 (±30) minutes, respectively. Betaine HCl was well tolerated by all subjects. In healthy volunteers with pharmacologically-induced hypochlorhydria, betaine HCl was effective at temporarily lowering gastric pH. The rapid onset and relatively short duration of gastric pH reduction gives betaine HCl the potential to aid the absorption of orally administered weakly basic drugs that exhibit pH-dependent solubility when administered under hypochlorhydric conditions

Evaluation of a Multidrug Assay for Monitoring Adherence to a Regimen for HIV Preexposure Prophylaxis in a Clinical Study, HIV Prevention Trials Network 073

ABSTRACT Daily oral tenofovir disoproxil fumarate (TDF)-emtricitabine (FTC) is a safe and effective intervention for HIV preexposure prophylaxis (PrEP). We evaluated the performance of a qualitative assay that detects 20 antiretroviral (ARV) drugs (multidrug assay) in assessing recent PrEP exposure (detection limit, 2 to 20 ng/ml). Samples were obtained from 216 Black men who have sex with men (208 HIV-uninfected men and 8 seroconverters) who were enrolled in a study in the United States evaluating the acceptability of TDF-FTC PrEP (165 of the uninfected men and 5 of the seroconverters accepted PrEP). Samples from 163 of the 165 HIV-uninfected men who accepted PrEP and samples from all 8 seroconverters were also tested for tenofovir (TFV) and FTC using a quantitative assay (detection limit for both drugs, 0.31 ng/ml). HIV drug resistance was assessed in seroconverter samples. The multidrug assay detected TFV and/or FTC in 3 (1.4%) of the 208 uninfected men at enrollment, 84 (40.4%) of the 208 uninfected men at the last study visit, and 1 (12.5%) of the 8 seroconverters. No other ARV drugs were detected. The quantitative assay confirmed all positive results from the multidrug assay and detected TFV and/or FTC in 9 additional samples (TFV range, 0.65 to 16.5 ng/ml; FTC range, 0.33 to 14.6 ng/ml). Resistance mutations were detected in 4 of the 8 seroconverter samples. The multidrug assay had 100% sensitivity and specificity for detecting TFV and FTC at drug concentrations consistent with daily PrEP use. The quantitative assay detected TFV and FTC at lower levels, which also might have provided protection against HIV infection