Population pharmacokinetics of the two enantiomers of tramadol and O -demethyl tramadol after surgery in children

International audienceBACKGROUND : Few data are available on the stereoselective pharmacokinetics of tramadol in children. The aim of this study was to develop a population pharmacokinetic model for the (+)- and (-)-enantiomers of tramadol and its O-demethyl tramadol metabolite (M1) in children.METHODS : Twenty-five children (1-8 yr) were included in this study. Tramadol was administered after surgery by continuous infusion (loading dose, 2 mg kg(-1) i.v. over 10 min followed by continuous infusion of 8 mg kg(-1) over 24 h). If pain relief was inadequate, additional 1 mg kg(-1) i.v. bolus doses of tramadol were given over 10 min. A two-compartment structural model was used with NONMEM.RESULTS : For both enantiomers of tramadol, weight was the only patient characteristic parameter showing significant covariate effects on clearance (CL). CL increased by 5.7-6.1 litre h(-1) between 8-12 and 13-16 kg, and by 2.4-3.3 litre h(-1) between 13-16 and 17-33 kg. The rate constants associated with the metabolite elimination [0.144 h(-1), (+)-M1 and 0.18 h(-1), (-)-M1] were smaller than the elimination rate constants of the parent drugs [0.243 h(-1), (+)-tramadol and 0.241 h(-1), (-)-tramadol], suggesting that the metabolite disposition was rate-limited by its elimination. The presence of two subpopulations of patients was suspected on the basis of the observed bimodal distributions of the AUC(M1)/AUC(tramadol) ratios.CONCLUSIONS : The results of this study combine relationships between tramadol CL and patient covariates that may be useful for dose adjustment. Polymorphism is likely to contribute to the interpatient variability observed in the AUC M1/AUC tramadol ratios

Insertion reactions of organochlorosilanes with cyclic ethers

Phenyl glycidyl ether and allyl glycidyl ether (3-phenoxy- and 3-allyloxy-1,2-epoxypropane) cause fission of the silicon---chlorine bonds in a number of alkylchlorosilanes to form chloro-substituted alkoxysilanes. Relative reactivities of cyclic ethers with chlorosilanes have been discussed. Structures of the adducts are suggested on the basis of their IR and proton magnetic resonance spectra

Moisture content and chloride ion effect on the corrosion behavior of fitting brass (gate valves) used as a connection of PVC’s conduits in aggressive sandy soil

The corrosion of four brasses EC1 and EC2 of ( α + β ) brass type while EC3 and EC4 are of α -brass type in the aggressive sandy soil collected in a suburban area of Essouira Morocco was studied. The original soil was characterized, and modified by adding the chloride ions or by increasing its moisture content. The corrosion behavior of these brasses in soil was investigated at ambient temperature using various electrochemical methods. The different alloy surfaces were examined by scanning electron microscopy, whereas the chemical composition was determined by EDS analysis. EIS measurements indicated that the corrosion rate of all brasses series increases with increasing the moisture content of the studied soil up to critical limit (30 wt%), then it starts to decrease with further increase of moisture content. It was found that the chemical composition of brass influences the corrosion rate, especially the presence of iron, Nickel and Arsenic. Furthermore, EC3 is always the most resistant among the other alloy even in a very aggressive environment containing the chloride ions with a concentration of 2%