Population pharmacokinetic analysis of risperidone and its metabolite and evaluation of effect of covariates on Pk parameters was written by Bootam, Sharath Babu;Kannadhasan, R.;Gummadi, Sridhar Babu. And the article was included in Natural Volatiles & Essential Oils in 2021.Electric Literature of C23H27FN4O3 This article mentions the following:
To characterize pharmacokinetic (PK) variability of risperidone and 9-OH risperidone using sparse sampling and to evaluate the effect of covariates on PK parameters. PK anal. used plasma samples collected from the Clin. Anti-psychotic 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. PK samples comprised risperidone and 9-OH risperidone concentrations from 20 subjects that were available for anal. Ages ranged from 18 to 93 years. Population PK sub models 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. A mixture model was incorporated with risperidone clearance (CL) sep. estimated for three subpopulations [poor metabolizer (PM), extensive metabolizer (EM) and intermediate metabolizer (IM)]. Age significantly affected 9-OH risperidone clearance. Population parameter estimates for CL in PM, IM and EM were 12.9, 36 and 65.4 l h-1 and parameter estimates for risperidone half-life in PM, IM and EM were 25, 8.5 and 4.7 h, resp. A 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. In the experiment, the researchers used many compounds, for example, 3-(2-(4-(6-Fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)ethyl)-9-hydroxy-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one (cas: 144598-75-4Electric Literature of C23H27FN4O3).
3-(2-(4-(6-Fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)ethyl)-9-hydroxy-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one (cas: 144598-75-4) belongs to isoxazole derivatives. Isoxazoles are aromatic heterocycles containing an N–O bond. Isoxazoles are commonly used as enaminoketone or β-diketone surrogate. Fe(CO)5 efficiently cleaves the N–O bond of fused isoxazolo-1,4-quinones to give the corresponding imines.All the common reducing reagents failed to open the isoxazole ring.Electric Literature of C23H27FN4O3
Referemce:
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem