The Western Scheldt Estuary (SE) 29.9 ng/g ww in benthic invertebrates and goby, from 0.08 to 6.9 ng/g ww in fish muscle, and from 15.0 t0 984 ng/g ww in fish liver. BDE 209 could only be detecled in eight liver samples trom the SE and levels ranged between 3.4 and 37.2 ng/g ww. PBDE profiles of the various sDecies at the ditferent locations were compared. Differences in prolile were attributed to different exposule and l0 differences in metabolism among species. Ratios bolween BDE 99 and 100 were found to be highly location and species dependent, which could be related to differences in melabolism. Some species, such as dab, plaice bib, and whiting, showed prelerential accumulation of PBDEs in lhe liver. Higher brominated congeners in general showed higher atfinity for liver than lor muscle tissue.

There is extensive literature documenting the bioaccumulation of persistent organic pollutants in the marine environment, but relatively little data are available on contamination pathways in aquaculture systems such as that for farmed salmon. In recent years,the salmon industry has grown significantly in Europe. This study reports on the determination of a wide range of polychlorinated biphenyls (PCBs), organochlorine pesticides, and polybrominated diphenyl ethers (PBDEs) in farmed and wild European Atlantic salmon fish, aquaculture feeds, and fish oils used to supplement the feeds. The study confirms previous reports of relatively high concentrations of PCBs and indicates moderate concentrations of organochlorine pesticides and PBDEs in farmed Scottish and European salmon. Concentrations of the selected persistent organic pollutants varied among the samples: PCBs (salmon, 145-460 ng/g lipid; salmon feeds, 76-1153 ng/g lipid; fish oils, 9-253 ng/g lipid), S DDTs (salmon, 5-250 ng/g lipid; salmon feeds, 34-52 ng/g lipid; fish oils, 11-218 ng/g lipid), and PBDEs (salmon, 1-85 ng/g lipid: salmon feeds, 8-24 ng/g lipid; fish oils, ND-13 ng/g lipid). Comparison of the samples for all groups of contaminants, except for HCHs, showed an increase in concentration in the order fish oil < feed < salmon. Homologue profiles were similar, with an increase in contribution of hepta- and octa-PCBs in the fish, and profiles of DDTs were similar in all three types of samples. With a constant contribution to the total PCB content, the ICES 7 PCBs appear to be reliable predictors of the PCB contamination profile through all the samples. For PBDEs, BDE 47 dominated the profiles, with no significant difference in the PBDE profiles for the three matrixes. Samples with higher PCB contents generally showed higher levels of the pesticide residues, but this was not the case with the PBDEs, indicating the existence of different pollution sources.

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Ibuprofen is a nonsteroidal anti-inflammatory agent that induces closure of the patent ductus arteriosus in neonates.• Few studies of ibuprofen pharmacokinetics have been performed and were limited to small groups of preterm infants, showing a large intersubject variability and an increase in clearance with either postnatal or gestational age. WHAT THIS STUDY ADDS• A population pharmacokinetic study was performed on 66 neonates to characterize the concentration-time courses of ibuprofen.• Ibuprofen clearance significantly increased from postnatal age day 1 to day 8, but not with gestational age.• A relationship was shown between ibuprofen area under the curve (AUC) and patent ductus arteriosus closure rate, and an effective threshold AUC was evidenced.• Dosing schemes were proposed as a function of postnatal age, to achieve this AUC and to improve the efficacy of treatment for patent ductus arteriosus in neonates. AIMSTo describe ibuprofen pharmacokinetics in preterm neonates with patent ductus arteriosus (PDA) and to establish relationships between doses, plasma concentrations and ibuprofen efficacy and safety. METHODSSixty-six neonates were treated with median daily doses of 10, 5 and 5 mg kg -1 of ibuprofen-lysine by intravenous infusion on 3 consecutive days. A population pharmacokinetic model was developed with NONMEM. Bayesian individual pharmacokinetic estimates were used to calculate areas under the curve (AUC) and to simulate doses. A logistic regression was performed on PDA closure. RESULTSIbuprofen pharmacokinetics were described by a one-compartment model with linear elimination. Mean population pharmacokinetic estimates with corresponding intersubject variabilities (%) were: elimination clearance CL = 9.49 ml h -1 (62%) and volume of distribution V = 375 ml (72%). Ibuprofen CL significantly increased with postnatal age (PNA): CL = 9.49*(PNA/96.3) 1.49 . AUC after the first dose (AUC1D), the sum of AUC after the three doses (AUC3D) and gestational age were significantly higher in 57 neonates with closing PDA than in nine neonates without PDA closure (P = 0.02). PDA closure was observed in 50% of the neonates when AUC1D < 600 mg l -1 h (or AUC3D < 900 mg l -1 h) and in 91% when AUC1D > 600 mg l -1 h (or AUC3D > 900 mg l -1 h) (P = 0.006). No correlation between AUC and side-effects could be demonstrated. CONCLUSIONSTo achieve these optimal AUCs, irrespective of gestational age, three administrations at 24 h intervals are recommended of 10, 5, 5 mg kg -1 for neonates younger than 70 h, 14, 7, 7 mg kg -1 for neonates between 70 and 108 h and 18, 9, 9 mg kg -1 for neonates between 108 and 180 h.

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