Safety, pharmacokinetics, pharmacodynamics, and plasma lipoprotein distribution of eritoran (E5564) during continuous intravenous infusion into healthy volunteers.

Eritoran, a structural analogue of the lipid A portion of lipopolysaccharide (LPS), is an antagonist of LPS in animal and human endotoxemia models. Previous studies have shown that low doses (350 to 3,500 microg) of eritoran have demonstrated a long pharmacokinetic half-life but a short pharmacodynamic half-life. The present study describes the safety, pharmacokinetics and pharmacodynamics, and lipid distribution profile of eritoran during and after a 72-h intravenous infusion of 500, 2,000, or 3,500 microg/h into healthy volunteers.

Sleep Problems Across the Life Cycle in Women.

Across the life cycle of women, the quality and quantity of sleep can be markedly impacted by internal (eg, hormonal changes and vasomotor symptoms) and external (financial and child-care responsibilities; marital issue) factors. This paper will outline some of the major phases of the life cycle in women that have been associated with sleep problems. The main messages from this paper include 1) that very little systematic, large-scale research has been performed in virtually every area reviewed; and 2) once identified, the sleep problem is generally best addressed by the standard therapeutic approach, except in the case of pregnant and lactating women in which concern for the fetus and child must be considered in the treatment decision.

Extended in vivo pharmacodynamic activity of E5564 in normal volunteers with experimental endotoxemia [corrected].

E5564 (alpha-D-glucopyranose) is a synthetic antagonist of bacterial endotoxin that has been shown to completely block human endotoxin response. Low doses of E5564 (0.35-3.

Patient populations in clinical trials of the efficacy and tolerability of donepezil in patients with vascular dementia.

There is increasing evidence to suggest that patients with vascular dementia (VaD) exhibit a cholinergic deficit. These patients may therefore benefit from treatment with cholinesterase (ChE) inhibitors such as donepezil. However, there are difficulties in accurately defining patients with VaD.

Role of integrative pharmacokinetic and pharmacodynamic optimization strategy in the management of Parkinson"s disease patients experiencing motor fluctuations with levodopa.

Parkinson's disease is a progressively debilitating motor neuron disease that affects the dopaminergic neurons within the nigral-striatal and surrounding pathways and which is characterized clinically by rigidity, resting tremor and bradykinesia with or without postural imbalance. Levodopa is the "gold standard" for the treatment and management of Parkinson's disease worldwide. However, following prolonged use of the drug, the "honey-moon" which was once enjoyed by patients on levodopa begins to wane.

An evaluation of the pharmacokinetics of donepezil HCl in patients with moderately to severely impaired renal function.

Aim: The aim of this study was to evaluate the pharmacokinetics of donepezil HCl (5 mg) in patients with moderately to severely impaired renal function (creatinine clearance: <30 ml min(-1) 1.73 m(-2)), following the administration of single oral doses.

Methods: This was an open-label, non-randomized study in patients with compromised renal function (n=11), and in age- and gender-matched healthy controls (n =11).

An evaluation of the pharmacokinetics of donepezil HCl in patients with impaired hepatic function.

Aim: The aim of this study was to evaluate the pharmacokinetic profile of donepezil HCl (5 mg) in patients with impaired hepatic function, following the administration of single oral doses.

Methods: This was an open-label, non-randomized study comparing the pharmacokinetic profile of donepezil in male volunteers with chronic compensated cirrhosis of the liver (n = 10) to that in healthy age- and sex-matched controls (n = 10). Each subject received a single 5 mg oral dose of donepezil.

The effect of multiple doses of donepezil HCl on the pharmacokinetic and pharmacodynamic profile of warfarin.

Aim: The aim of the study was to examine the pharmacokinetic and pharmacodynamic profiles of single doses of warfarin (25 mg) following administration alone, and in combination with multiple doses of donepezil HCl (10 mg day(-1)) in healthy volunteers.

Methods: This was an open-label, two-period crossover study in 12 healthy male volunteers, aged 18-55 years, who were randomized to one of the following treatment groups: (A) donepezil administered for 19 consecutive days with a single dose of warfarin administered on day 14. On day 20, there was a 21-day washout period after which a single dose of warfarin was again administered, and (B) an initial 13-day period with no medication, then a single dose of warfarin administered alone on day 14, followed by a 14-day washout period.

Concurrent administration of donepezil HCl and digoxin: assessment of pharmacokinetic changes.

Aim: The aim of this study was to examine the pharmacokinetics of donepezil HCl and digoxin separately, and in combination, following administration of single oral doses. Changes in cardiac conduction parameters following drug administration were also assessed.

Methods: This was an open-label, randomized, three-period crossover study in healthy male volunteers (n=12).

Concurrent administration of donepezil HCl and theophylline: assessment of pharmacokinetic changes following multiple-dose administration in healthy volunteers.

Aim: The aim of the study was to evaluate the pharmacokinetics of theophylline administered alone, and in combination with donepezil HCl, following multiple-dose administration of both drugs in healthy volunteers.

Methods: This was an open-label, randomized, two-period crossover study in healthy male volunteers (n=12). During each treatment period, subjects received either titrated-dose theophylline alone, or in combination with donepezil (5 mg, once daily) for 10 consecutive days.

Concurrent administration of donepezil HCl and ketoconazole: assessment of pharmacokinetic changes following single and multiple doses.

Aim: The aim of this study was to examine the pharmacokinetics of donepezil HCl and ketoconazole separately, and in combination, following administration of single and multiple oral doses.

Methods: This was an open-label, randomized, three-period crossover study in healthy volunteers (n=21). During each treatment period, subjects received single daily doses of either donepezil HCl (5 mg), ketoconazole (200 mg), or a combination of both drugs for 7 consecutive days.

Concurrent administration of donepezil HCl and cimetidine: assessment of pharmacokinetic changes following single and multiple doses.

Aim: The aim of this study was to examine the pharmacokinetics of donepezil HCl and cimetidine separately, and in combination, following administration of multiple oral doses.

Methods: This was an open-label, randomized, three-period crossover study in healthy male volunteers (n=19). During each treatment period, subjects received single daily doses of either donepezil HCl (5 mg), cimetidine (800 mg), or a combination of both drugs for 7 consecutive days.

Metabolism and elimination of 14C-donepezil in healthy volunteers: a single-dose study.

Aim: The aim of this study was to investigate the metabolism and elimination of donepezil HCl in humans, following the administration of a single 5 mg (liquid) oral dose containing a mixture of unlabelled and 14C-labelled donepezil.

Methods: This was an open-label, non-randomized study in healthy male volunteers (n = 8). Characterization of donepezil metabolism and elimination was performed by analysing blood, urine and faecal samples collected over a 10-day period following drug administration.

Pharmacokinetic and pharmacodynamic profile of donepezil HCl following evening administration.

Aims: The primary objective of this study was to characterize the pharmacokinetics and pharmacodynamics of single daily doses of donepezil (5 and 10 mg) each evening for 28 consecutive days. A secondary objective was to measure the plasma protein binding of donepezil at steady state.

Methods: This was a double-blind, randomized, multiple-dose study in healthy male (n=13) and female (n=3) volunteers.

Pharmacokinetic and pharmacodynamic profile of donepezil HCl following multiple oral doses.

Aim: The aim of this study was to characterize the pharmacokinetics and pharmacodynamics of donepezil HCl, a new, chemically distinct and specific acetylcholinesterase (AChE) inhibitor for the treatment of Alzheimer's disease, following multiple-dose administration.

Methods: This was a double-blind, randomized, placebo-controlled, multiple-dose study in healthy male volunteers (n=27). Three dose levels were investigated in sequential order: 1, 3 and 5 mg.

Pharmacokinetic and pharmacodynamic profile of donepezil HCl following single oral doses.

Aim: The aim of this study was to characterize the pharmacokinetic and pharmacodynamic profile of donepezil HCl, a chemically distinct and specific acetylcholinesterase (AChE) inhibitor for the treatment of Alzheimer's disease, following administration of single oral doses.

Methods: This was a double-blind, randomized, single-dose, placebo-controlled, sequential-group, ascending-dose study in healthy male volunteers (n = 48). Six dose levels were investigated, ranging from 0.

Further clinical studies of curdlan sulfate (CRDS)--an anti-HIV agent.

Curdlan sulfate (CRDS) is a semi-synthetic sulfated polysaccharide which inhibits the attachment of HIV to T-cells, and also has intracellular anti-HIV activity. In Phase I clinical trials, CRDS was found in 4 hr i.v.