BackgroundManagement of patients with gastro-oesophageal reflux disease (GORD) can be assisted by information predicting the likely response to proton pump inhibitor (PPI) treatment. The aim was to undertake a study of GORD patients designed to approximate ordinary clinical practice that would identify patient characteristics predicting symptomatic response to pantoprazole treatment.Methods1888 patients with symptoms of GORD were enrolled in a multicentre, multinational, prospective, open study of 8 weeks pantoprazole treatment, 40 mg daily. Response was assessed by using the ReQuest™ questionnaire, by the investigator making conventional clinical enquiry and by asking patients about their satisfaction with symptom control. Factors including pre-treatment oesophagitis, gender, age, body mass index (BMI), Helicobacter pylori status, anxiety and depression, and concurrent IBS symptoms were examined using logistic regression to determine if they were related to response, judged from the ReQuest™-GI score.ResultsPoorer treatment responses were associated with non-erosive reflux disease, female gender, lower BMI, anxiety and concurrent irritable bowel syndrome symptoms before treatment. No association was found with age, Helicobacter pylori status or oesophagitis grade. Some reflux-related symptoms were still present in 14% of patients who declared themselves 'well-satisfied' with their symptom control.ConclusionsSome readily identifiable features help to predict symptomatic responses to a PPI and consequently may help in managing patient expectation. ClinicalTrial.gov identifier: NCT00312806.
SUMMARY BackgroundAlthough erosive gastro-oesophageal reflux disease (GERD) is a highly prevalent condition, there is no specific, valid, reliable and sensitive questionnaire that allows evaluating treatment-induced changes in health-related quality of life (HRQoL).
Background and ObjectiveSchizophrenia and Alzheimer’s disease are characterised by abnormalities in glutamatergic pathways related to N-methyl-d-aspartate receptor hypofunction. Glycine is an N-methyl-d-aspartate receptor co-agonist; inhibition of glycine transporter 1 may improve N-methyl-d-aspartate receptor function. This phase I, randomised, two-part study evaluated the safety, tolerability and pharmacokinetic profile of BI 425809, a novel glycine transporter 1 inhibitor, in healthy male and female volunteers.MethodsPart 1 evaluated BI 425809 10, 25, 50 or 75 mg once daily or 75 mg twice daily in young subjects, and 25 mg or 50 mg once daily in elderly subjects. Each dose group comprised 12 subjects who received BI 425809 (n = 9) or placebo (n = 3) for 14 days (day 1: single dose; days 4–14: multiple dosing). Part 2 compared pharmacokinetic profiles in 12 subjects who received a single dose of BI 425809 25 mg in the morning and evening.ResultsPharmacokinetic profiles were similarly shaped for all dose groups. Median time to maximum plasma concentration was 3.0–4.5 h with steady state being reached between days 6 and 10. Pharmacokinetic parameters demonstrated dose linearity at the predicted therapeutic exposure range of BI 425809 ≤ 25 mg once daily, but increased less than dose proportionally for ≥ 50 mg once daily. All reported adverse events were of mild-to-moderate intensity, 51/84 (61%; part 1) subjects had one or more treatment-related adverse event, no serious adverse events occurred and no dose dependency was observed.ConclusionsPharmacokinetic properties support both morning and evening dosing. BI 425809 was generally well tolerated at all tested doses.Clinicaltrials.gov identifierNCT02337283.Electronic supplementary materialThe online version of this article (10.1007/s40261-018-0660-2) contains supplementary material, which is available to authorized users.
1. Famotidine, a new histamine H2‐receptor antagonist was administered intravenously (20 mg) to 22 patients with end stage renal disease during a dialysis free interval (n = 6) and during different blood purification processes including haemodialysis (HD; n = 4), intermittent haemofiltration (HF; n = 4), continuous haemofiltration (CHF; n = 4) and continuous ambulatory peritoneal dialysis (CAPD; n = 4). The plasma, the dialysate/filtrate and the urine concentrations of famotidine were analysed by h.p.l.c. 2. In addition, intra‐gastric pH was measured by a long‐term‐pH probe in seven patients with renal failure and in six patients with normal renal function (control group) following 20 mg famotidine. 3. A 7 to 10 fold prolongation of famotidine's elimination half‐life (27.2 +/‐ 8.5 h; mean +/‐ s.d.) was observed in patients with renal failure as compared with the half‐life (2.6‐3.6 h) in subjects with normal renal function. 4. Total body clearance (CL) and volume of distribution (V) were found to be 33.5 +/‐ 10.1 ml min‐1 and 1.3 +/‐ 0.7 l kg‐1, respectively in patients with end‐ stage renal failure. 5. Blood purification processes have shown considerable variation in clearing famotidine from the body: 16.4 +/‐ 8.9 and 6.0 +/‐ 2.9% of the administered dose in HD with polysulphone and cuprophan membranes respectively, 7.7 +/‐ 5.2% in HF with a polyacrylonitrile membrane (each for 5 h), 4.5 +/‐ 1.1% in CAPD and 16.2 +/‐ 4.9% in CHF with a polysulphone membrane within 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)
Context: Intranasal fentanyl spray (INFS) was developed for the treatment of breakthrough pain in cancer patients using an alternative route of administration. Objective: The aim of this clinical study was to investigate the pharmacokinetic (PK) profile and bioavailability of INFS in healthy subjects compared to oral transmucosal fentanyl citrate (OTFC). Materials and methods: In a randomized, single-center, open-label, two-way crossover PK study, 24 subjects (12 male, 12 female, mean age 25.2 years) received INFS (single-dose delivery system 200 mg/100 ml) and OTFC (buccal lozenge, 200 mg). Naltrexone was given to prevent potential adverse reactions. Frequent plasma samples were taken up to 96 h and analyzed by LC-MS/MS with a lower limit of quantitation of 25 pg/ml. Primary PK parameter was the area under the fentanyl plasma concentration-time curve (AUC 0-inf ). Results: Compared to OTFC, a much faster absorption rate was observed for INFS which was supported by the much earlier appearance of detectable fentanyl plasma levels and a shorter T max . At 15 min post-dose, the mean plasma fentanyl levels reached 602 pg/ml for INFS and 29 pg/ml for OTFC. Significantly higher C max and AUC values were obtained with INFS compared to OTFC. Although administered for 15 min, consumption of OTFC was incomplete in many incidences ($70%) upon visual inspection. No safety concerns were identified for fentanyl administration in combination with oral naltrexone. Discussion and conclusion: One dose of INFS gives significantly higher plasma fentanyl levels and significantly higher bioavailability than OTFC based on dose-normalized AUC. KeywordsBreakthrough cancer pain, drug delivery system, incomplete consumption of oral transmucosal fentanyl citrate, pharmacokinetics, single-dose delivery system History
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