Human influenza virus challenge identifies cellular correlates of protection for oral vaccination.

Developing new influenza vaccines with improved performance and easier administration routes hinges on defining correlates of protection. Vaccine-elicited cellular correlates of protection for influenza in humans have not yet been demonstrated. A phase-2 double-blind randomized placebo and active (inactivated influenza vaccine) controlled study provides evidence that a human-adenovirus-5-based oral influenza vaccine tablet (VXA-A1.

Performance of BioFire array or QuickVue influenza A + B test versus a validation qPCR assay for detection of influenza A during a volunteer A/California/2009/H1N1 challenge study.

Background: Influenza places a significant burden on global health and economics. Individual case management and public health efforts to mitigate the spread of influenza are both strongly impacted by our ability to accurately and efficiently detect influenza viruses in clinical samples. Therefore, it is important to understand the performance characteristics of available assays to detect influenza in a variety of settings.

Landscape of coordinated immune responses to H1N1 challenge in humans.

Influenza is a significant cause of morbidity and mortality worldwide. Here we show changes in the abundance and activation states of more than 50 immune cell subsets in 35 individuals over 11 time points during human A/California/2009 (H1N1) virus challenge monitored using mass cytometry along with other clinical assessments. Peak change in monocyte, B cell, and T cell subset frequencies coincided with peak virus shedding, followed by marked activation of T and NK cells.

QT and QTc interval with standard and supratherapeutic doses of darifenacin, a muscarinic M3 selective receptor antagonist for the treatment of overactive bladder.

Prolongation of QT interval on an electrocardiogram is a valuable predictor of a drug's ability to cause potentially fatal ventricular tachyarrhythmia (torsades de pointes). Darifenacin is a muscarinic M3 selective receptor antagonist developed for the treatment of overactive bladder, a debilitating condition that is particularly prevalent in the older population. This 7-day, randomized, parallel-group study (n=188) measured QT/QTc interval in healthy volunteers receiving once-daily darifenacin at steady-state therapeutic (15 mg) and supratherapeutic (75 mg) doses, alongside controls receiving placebo or moxifloxacin (positive control, 400 mg) once daily.

Single-dose pharmacokinetics and tolerability of pegylated interferon-alpha2b in young and elderly healthy subjects.

Aims: To assess the single-dose pharmacokinetics and tolerability of pegylated interferon-alpha2b (PEG-Intron) in young and elderly healthy subjects.

Methods: In this parallel-design study, a single 1 microg x kg(-1) PEG-Intron dose was given subcutaneously to 24 subjects in the age groups 20-45, 65-69, 70-74 and 75-80 years (n = 6/group). Blood sampling and tolerability assessments were performed up to 168 h postdose.

Ribavirin dosing in chronic hepatitis C: application of population pharmacokinetic-pharmacodynamic models.

Background: Combination therapy of ribavirin with interferon alfa-2b and pegylated interferon alfa-2b is currently approved for the treatment of chronic hepatitis C. Approved ribavirin dosages vary from a fixed dosage of 800 mg/d to as much as 1200 mg/d on the basis of body weight.

Objective: Our objective was to evaluate ribavirin dosing strategies by comparison of their relative efficacy and toxicity profiles.

Single-dose pharmacokinetics and safety of pegylated interferon-alpha2b in patients with chronic renal dysfunction.

This study evaluates the pharmacokinetics and safety of pegylated interferon-alpha2b (PEG-Intron) following a single-dose subcutaneous injection into subjects with normal renal function, subjects with chronic renal impairment, and patients on hemodialysis. In this open-label, single-dose, parallel group study, subjects were divided into five groups according to their degree of renal function: four groups as defined by measured creatinine clearance and a fifth hemodialysis dependent group. They received 1 microg/kg PEG-Intron subcutaneously after a 10-hour fast.

Pharmacodynamic interaction between the new selective cholesterol absorption inhibitor ezetimibe and simvastatin.

Aims: The primary aims of these two single-centre, randomized, evaluator-blind, placebo/positive-controlled, parallel-group studies were to evaluate the potential for pharmacodynamic and pharmacokinetic interaction between ezetimibe 0.25, 1, or 10 mg and simvastatin 10 mg (Study 1), and a pharmacodynamic interaction between ezetimibe 10 mg and simvastatin 20 mg (Study 2). Evaluation of the tolerance of the coadministration of ezetimibe and simvastatin was a secondary objective.

Desloratadine has no clinically relevant electrocardiographic or pharmacodynamic interactions with ketoconazole.

Objective: This study was performed to assess the electrocardiographic safety and pharmacokinetics of desloratadine in combination with the CYP3A4 inhibitor ketoconazole.

Design: A randomised, placebo-controlled, third-party-blind, 2-way crossover study.

Participants: 24 healthy volunteers (12 men, 12 women; age 19 to 50 years).

Lack of clinically relevant interaction between desloratadine and erythromycin.

Objective: To evaluate the bioavailability, cardiac safety and tolerability of desloratadine when given in combination with the CYP3A4 inhibitor erythromycin.

Design: A randomised, 2-way crossover, placebo-controlled, third party-blind, multiple dose study.

Participants: 24 healthy volunteers (12 men, 12 women) aged 19 to 46 years.

Effect of race and sex on single and multiple dose pharmacokinetics of desloratadine.

Objective: This study was designed to characterise the single and multiple dose pharmacokinetic profile of desloratadine, a new antihistamine, and its main metabolite, 3-hydroxy (3-OH) desloratadine, in healthy volunteers differing in sex and race.

Design: An open-label, parallel-group, single- and multiple-dose pharmacokinetic trial.

Intervention: A single 7.

A pharmacokinetic profile of desloratadine in healthy adults, including elderly.

Objective: To characterise the pharmacokinetic profile of desloratadine and its main metabolite, 3-hydroxy (3-OH) desloratadine, in a patient population representative of the population studied in the desloratadine clinical efficacy and safety studies, including the elderly.

Design: A multicentre, multidose, open-label pharmacokinetic trial.

Participants: 113 healthy adult volunteers (57 men, 56 women; 95 White, 18 Black) were enrolled, and 112 completed the study.

Oral bioavailability of desloratadine is unaffected by food.

Objective: To determine the effect of coadministration of food on the bioavailability of oral desloratadine.

Design: A randomised, open-label, single dose crossover study in which healthy adults received a single, oral dose of desloratadine 7.5mg, 50% greater than the recommended dose of 5mg, under fed or fasted conditions and were then crossed over to receive the other treatment regimen.

Desloratadine demonstrates dose proportionality in healthy adults after single doses.

Objective: To evaluate the dose proportionality and linearity and pharmacokinetic profile of desloratadine after single oral doses over the range of 5 to 20mg.

Design: Single centre, randomised, open-label, 4-way crossover study in which healthy adults received single doses of desloratadine (5, 7.5, 10 and 20mg) in 4 different treatment periods.

Grapefruit juice reduces the oral bioavailability of fexofenadine but not desloratadine.

Background: Certain foods, such as grapefruit juice, are known to substantially alter the bioavailability of some drugs. These effects may be mediated by interactions with enzyme systems, such as cytochrome P450, or with active transporter systems, such as P-glycoprotein and organic anion transporting polypeptides.

Objective: To assess the effect of consumption of grapefruit juice on the oral bioavailability of two nonsedating antihistamines, fexofenadine and desloratadine.

Disposition of the selective cholesterol absorption inhibitor ezetimibe in healthy male subjects.

Ezetimibe [SCH 58235; 1-(4-fluorophenyl)-3(R)-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4(S)-(4-hydroxyphenyl)-2-azetidinone], a selective cholesterol absorption inhibitor, is being developed for the treatment of primary hypercholesterolemia. The absorption, metabolism, and excretion of ezetimibe were characterized in eight healthy male volunteers in this single-center, single-dose, open-label study. Subjects received a single oral 20-mg dose of [14C]ezetimibe (approximately 100 microCi) with 200 ml of noncarbonated water after a 10-h fast.

Pharmacokinetics of Loratadine in Pediatric Subjects.

The pharmacokinetics of loratadine, a new nonsedating antihistamine, was studied in 14 pediatric volunteers between the ages of 8 to 12 years. In an open-label design, one volunteer (with body weight less than 30 kg) received 5 mg of loratadine syrup and 13 volunteers (with body weights greater than 30 kg) received 10 mg of loratadine syrup. Blood samples were collected up to 72 h after dosing.

Multiple-Dose Pharmacokinetics of Ceftibuten in Healthy Adults and Geriatric Volunteers.

The steady-state pharmacokinetics of ceftibuten, an orally active cephalosporin were investigated in 12 healthy male volunteers (19--38 years) and in 12 geriatric volunteers (65--76 years). Each received one 200-mg ceftibuten capsule every 12 h on days 1--3 and one capsule in the morning on day 4. Plasma and urine samples were collected at various times on days 1--4 and assayed by high-pressure liquid chromatographic method for ceftibuten and ceftibuten-trans, a conversion product.