MAP Bayesian modelling combining striatal dopamine receptor occupancy and plasma concentrations to optimize antipsychotic dose regimens in individual patients was written by Ismail, Mohamed;Straubinger, Thomas;Uchida, Hiroyuki;Graff-Guerrero, Ariel;Nakajima, Shinichiro;Suzuki, Takefumi;Caravaggio, Fernando;Gerretsen, Philip;Mamo, David;Mulsant, Benoit H.;Pollock, Bruce G.;Bies, Robert. And the article was included in British Journal of Clinical Pharmacology in 2022.Computed Properties of C23H27FN4O3 This article mentions the following:
Aims : Develop a robust and user-friendly software tool for the prediction of dopamine D2 receptor occupancy (RO) in patients with schizophrenia treated with either olanzapine or risperidone, in order to facilitate clinician exploration of the impact of treatment strategies on RO using sparse plasma concentration measurements. Methods : Previously developed population pharmacokinetic models for olanzapine and risperidone were combined with a pharmacodynamic model for D2 RO and implemented in the R programming language. Maximum a posteriori Bayesian estimation was used to provide predictions of plasma concentration and RO based on sparse concentration sampling. These predictions were then compared to observed plasma concentration and RO. Results : The average (standard deviation) response times of the tools, defined as the time required for the application to predict parameter values and display the output, were 2.8 (3.1) and 5.3 (4.3) seconds for olanzapine and risperidone, resp. The mean error (95% confidence interval) and root mean squared error (95% confidence interval) of predicted vs. observed concentrations were 3.73 ng/mL (-2.42-9.87) and 10.816 ng/mL (6.71-14.93) for olanzapine, and 0.46 ng/mL (-4.56-5.47) and 6.68 ng/mL (3.57-9.78) for risperidone and its active metabolite (9-OH risperidone). Mean error and root mean squared error of RO were -1.47% (-4.65-1.69) and 5.80% (3.89-7.72) for olanzapine and -0.91% (-7.68-5.85) and 8.87% (4.56-13.17) for risperidone. Conclusion : Our monitoring software predicts concentration-time profiles and the corresponding D2 RO from sparsely sampled concentration measurements in an accessible and accurate form. 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: 144598-75-4Computed Properties 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. Isoxazole rings are found in some natural products, such as ibotenic acid and muscimol. Isoxazoles are potent isosteres of pyridine and have been found to inhibit voltage-gated sodium channels for pain control, for the construction of tetracycline antibiotic derivatives, and as a therapeutic agent for depression.Computed Properties of C23H27FN4O3
Referemce:
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem