No abstract

No abstract

Propranolol has become the first choice therapy for complicated Infantile Hemangiomas (IH). The pharmacokinetics of propranolol were evaluated after repeated oral administration of a new pediatric solution of propranolol at 3 mg kg−1 day−1 given twice daily (BID) in infants (77‐243 days) with IH. A population model was built to describe the pharmacokinetics of propranolol in infants and to simulate different dosing regimens. One hundred and sixty‐seven plasma concentrations from 22 infants were used in the population analysis. Weight effect was tested on apparent clearance and volume of distribution. Monte‐Carlo simulations were performed for 4 dosing regimens: BID dosing with irregular or strict 12‐hour intervals and 2 different 3 time daily dosing (TID) regimens. The best model was a one‐compartment model with first‐order absorption and elimination rates. The weight affected the clearance but not the volume. Typical oral clearance was estimated at 3.06 L hour−1 kg−1 (95% CI: 1.14‐8.61 L hour−1 kg−1), close to adult clearance data. When regular BID dosing was compared to TID or irregular BID regimens, simulated median Cmin and Cmax were <20% different. To conclude, a model using a weight allometric function on clearance was established and confirmed that the dose in mg/kg should be used without adaptation by range of age in treatment of complicated IH. The simulations support the use of a BID dosing preferably to a TID dosing thanks to close Cmin and Cmax at steady state between both regimen and showed the possibility of irregular BID dosing, allowing early administration in the evening when needed.

Context. Coronagraphic techniques are required to observe substellar mass companions close to nearby bright stars by direct imagery. Phase mask coronagraphs are particularly interesting because they give access to the innermost regions. While the principle of the first such concept was validated experimentally a decade ago, the achieved brightness attenuation was too low to be conclusive, probably due to the imperfect thickness profile of the mask. Aims. We have manufactured and tested a second-generation Roddier & Roddier coronagraph in preparation for the development of more elaborate phase mask designs, planned to be used in the future European Extremely Large Telescope. Methods. A monolithic phase mask was made by ion beam machining. Experimentally obtained coronagraphic images were compared with simulated images. Results. Good agreement with theory was obtained. A peak attenuation of 216 was achieved, and a contrast of ∼10 −5 was measured at 5.7 λ/D. The results exploring contrasts obtained at different distances from the star for different mask dimensions are particularly interesting, confirming predictions made in the literature.

No abstract