WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Risperidone metabolism is affected by blocking CYP2D6 and CYP3A4 (in CYP2D6 poor metabolizers) metabolizing enzymes.• Age affects risperidone disposition and renal function affects elimination of 9-hydroxy-risperidone (primary active metabolite). WHAT THIS STUDY ADDS• The detection of a systematic shift in estimated apparent clearance in the African-American population (it is not clear if there are biological or sociological contributors), and a shift in the clearance rate of risperidone based on concomitant administration of paroxetine, manifested as a change in assignment to a different metabolizer subpopulation group that may be primarily related to CYP2D6 metabolizer status. • The study shows an age-related decrement in 9-hydroxy-risperidone clearance across a wide range of ages.• Information on the nature of the pharmacokinetic variability with risperidone when used in a typical clinical patient population.• There are significant differences in the absolute values as well as the assignment to metabolizer status across race and concomitant paroxetine administration. AIMSTo characterize pharmacokinetic (PK) variability of risperidone and 9-OH risperidone using sparse sampling and to evaluate the effect of covariates on PK parameters. METHODSPK analysis used plasma samples collected from the Clinical Antipsychotic Trials of Intervention Effectiveness. A nonlinear mixed-effects model was developed using NONMEM to describe simultaneously the risperidone and 9-OH risperidone concentration-time profile. Covariate effects on risperidone and 9-OH risperidone PK parameters were assessed, including age, weight, sex, smoking status, race and concomitant medications. RESULTSPK samples comprised 1236 risperidone and 1236 9-OH risperidone concentrations from 490 subjects that were available for analysis. Ages ranged from 18 to 93 years. Population PK submodels for both risperidone and 9-OH risperidone with first-order absorption were selected to describe the concentration-time profile of risperidone and 9-OH risperidone. CONCLUSIONSA one-compartment mixture model with first-order absorption adequately described the risperidone and 9-OH risperidone concentrations. Age was identified as a significant covariate on 9-OH risperidone clearance in this study.
Due to the rapid development of the nuclear power industry, and consequently, the nuclear accident in Fukushima, much attention has been paid to novel materials for the efficient and rapid separation, removal and recovery of nuclear fuel associated radionuclides from aqueous solutions. Herein, a novel mesoporous material, dihydroimidazole functionalized SBA-15 (DIMS), was synthesized via a postgrafting method and used as an efficient sorbent for the extraction of U(VI) from aqueous solution. The synthesized material was found to possess highly ordered mesoporous structures with a large surface area and a uniform pore diameter. The sorption tests under various conditions demonstrated that the sorption of U(VI) by DIMS was fast, with an equilibrium time of less than 10 min. Additionally, the maximum sorption capacity reached 268 mg g À1 at pH 5.0 AE 0.1. Changes in the solid-to-liquid ratio (m sorbent /V solution ) did not have any remarkable effect on the U(VI) sorption. Besides, the sorbed U(VI) can be easily desorbed by 0.01 mol L À1 or more concentrated HNO 3 solution, resulting in a U(VI) solution with a concentration factor of 300 at a solid-liquid ratio as low as 0.013 g L À1 . The reclaimed sorbent can be reused with no obvious decrease in the sorption capacity. The selectivity of the DIMS sorbent for U(VI) ions was found to be fairly desirable by the sorption tests with the solutions containing a range of competing metal ions.
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