Epidural infusions (0.2-0.4 mg.kg(-1).h(-1) ropivacaine) provided satisfactory pain relief in neonates and infants under 1 year. As plasma concentrations of unbound ropivacaine were not influenced by the duration of the infusion, ropivacaine can be safely used for postoperative epidural infusion for 48-72 h. Levels of unbound ropivacaine were higher in the neonates than in the infants, but were below threshold concentrations for CNS toxicity in adults (> or =0.35 mg.l(-1)). This should not preclude the use of ropivacaine infusions in neonates but suggests a need for caution during the first weeks of life.

We studied the pharmacokinetics after caudal block of ropivacaine (2 mg ml-1, 1 ml kg-1) performed in 20 children aged 1-8 yr undergoing subumbilical surgery, in this open, non-comparative, multicentre study. Venous blood samples were collected up to 12-36 h. The mean (SD) peak plasma concentration, 0.47 (0.16) mg litre-1, was achieved after 12-249 min. The free fraction was 5% and the highest individual peak plasma concentration of free ropivacaine was 0.04 mg litre-1. Clearance was 7.4 (1.9) ml min-1 kg-1 and the terminal half-life 3.2 (0.8) h. Thus, the free plasma concentrations of ropivacaine were well below those associated with toxic symptoms in adults and the capacity to eliminate ropivacaine seems to be well developed in this age group. In this open study of 20 patients, ropivacaine was well tolerated and provided satisfactory postoperative pain relief without observable motor block.

No abstract

The beta‐site amyloid precursor protein cleaving enzyme‐1 (BACE‐1) initiates the generation of amyloid‐β (Aβ), and the amyloid cascade leading to amyloid plaque deposition, neurodegeneration, and dementia in Alzheimer's disease (AD). Clinical failures of anti‐Aβ therapies in dementia stages suggest that treatment has to start in the early, asymptomatic disease states. The BACE‐1 inhibitor CNP520 has a selectivity, pharmacodynamics, and distribution profile suitable for AD prevention studies. CNP520 reduced brain and cerebrospinal fluid (CSF) Aβ in rats and dogs, and Aβ plaque deposition in APP‐transgenic mice. Animal toxicology studies of CNP520 demonstrated sufficient safety margins, with no signs of hair depigmentation, retina degeneration, liver toxicity, or cardiovascular effects. In healthy adults ≥ 60 years old, treatment with CNP520 was safe and well tolerated and resulted in robust and dose‐dependent Aβ reduction in the cerebrospinal fluid. Thus, long‐term, pivotal studies with CNP520 have been initiated in the Generation Program.

Following a caudal block with ropivacaine 2 mg x kg(-1) plasma concentrations of unbound ropivacaine were well below threshold levels for toxicity in adults. Apparent volume of distribution is unchanged, apparent unbound clearance increases and the terminal half-life decreases with age in 0-12-month-old neonates and infants. The postoperative pain management provided adequate analgesia and was well tolerated.