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In this paper, we used CALYPSO program which is conjuncted with DFT to investigate Li doped small-sized neutral Bn clusters. From ground-state and low energy structures, the properties and geometric significance of Li-doped boron clusters are greatly affected. Except for LiB9, which adds a B atom on preceding LiB8 boron wheel, the ground-state clusters of LiBn are formed by replacing the terminal boron atom of the Bn+1 clusters in the same size with a Li atom or by adding a Li atom to the Bn clusters. The transition point from 2 to 3D configuration of LiBn clusters appears at n = 5. The stability of LiBn clusters was analyzed by calculating the average binding energy, Gibbs free energy, first-order differential energy, second-order differential energy, HOMO–LUMO gap (the energy gap between the highest occupied and lowest unoccupied molecular orbital) and charge transfer. The results show that the LiB11 cluster with excellent symmetry and planar structure is the relative most stable structure. Molecular orbital and chemical bonding analysis indicated that the main reason for the stability of the LiB11 cluster is mainly due to the strong s-p bonding of B–B. [ABSTRACT FROM AUTHOR]

Objectives: Several population pharmacokinetics (popPK) models for polymyxin B have been constructed to optimize therapeutic regimens. However, their predictive performance remains unclear when extrapolated to different clinical centers. Therefore, this study aimed to evaluate the predictive ability of polymyxin B popPK models. Methods: A literature search was conducted, and the predictive performance was determined for each selected model using an independent dataset of 20 patients (92 concentrations) from the Third Xiangya Hospital. Prediction- and simulation-based diagnostics were used to evaluate model predictability. The influence of prior information was assessed using Bayesian forecasting. Results: Eight published studies were evaluated. In prediction-based diagnostics, the prediction error within ± 30% was over 50% in two models. In simulation-based diagnostics, the prediction- and variability-corrected visual predictive check (pvcVPC) showed satisfactory predictivity in three models, while the normalized prediction distribution error (NPDE) tests indicated model misspecification in all models. Bayesian forecasting demonstrated a substantially improvement in the model predictability even with one prior observation. Conclusion: Not all published models were satisfactory in prediction- and simulation-based diagnostics; however, Bayesian forecasting improved the predictability considerably with priors, which can be applied to guide polymyxin B dosing recommendations and adjustments for clinicians. [ABSTRACT FROM AUTHOR]

We had developed a visible light-catalyzed green synthesis method of 3-position substituted 3,4-dihydroisoquinoline-1(2H)-one compounds without metal participation, and initially proposed the reaction mechanism of visible light-catalyzed free radical involvement. In order to further verify the reliability of the proposed mechanism, density functional theory was used to analyze the structures involved in the reaction process. The theoretical results rationalized the experimental observations well and provided deeper insight into the mechanism. In addition, the photocatalytic reaction was further recognized by measuring the emission spectrum and absorption spectrum of the reaction system. [ABSTRACT FROM AUTHOR]

Delayed or missed doses are unavoidable in clinical practice and remain as a challenge that threatens a patient's health and quality-of-life, especially in the pharmacotherapy of chronic disease treatment. Unfortunately, information or guidance concerning the management of delayed or missed doses is scarce, precluding clinicians or clinical pharmacologists from instructing patients in a precision dosing manner. It is therefore urgent to develop remedial strategies to inform patients of alternative dosing regimens in compensation for the loss of efficacy due to delayed or missed doses and minimize unintended clinical consequences. Studies aiming to establish remedial regimens have been conducted since the 1980s for oral contraceptives and antihypertensive agents, using the controlled substitution of placebos for active medications. However, it appeared to be unethical in many areas of pharmacotherapy due to deliberately discontinuing or restarting the medication. Alternatively, pharmacometric modeling and simulation offers an opportunity to investigate the effect of various non-adherence scenarios on pharmacokinetic profiles and establish the optimum remedial dosing regimen in a time-effective and systematical way. This review provides a general overview of procedures and strategies on how to develop remedial dosing regimens based on pharmacometric approaches through the scrutiny of case examples in the literature. [ABSTRACT FROM AUTHOR]

Purpose: Numerous studies have been conducted on the population pharmacokinetics of tacrolimus in adult renal transplant recipients. It has been reported that the cytochrome P450 (CYP) 3A5 genotype is an important cause of variability in tacrolimus pharmacokinetics. However, the predictive performance of population pharmacokinetic (PK) models of tacrolimus should be evaluated prior to their implementation in clinical practice. The aim of the study reported here was to test the predictive performance of these published PK models of tacrolimus.Methods: A literature search of the PubMed and Web of Science databases ultimately led to the inclusion of eight one-compartment models in our analysis. We collected a total of 1715 trough concentrations from 174 patients. Predictive performance was assessed based on visual and numerical comparison bias and imprecision and by the use of simulation-based diagnostics and Bayesian forecasting.Results: Of the eight one-compartment models assessed, seven showed better predictive performance in CYP3A5 extensive metabolizers in terms of bias and imprecision. Results of the simulation-based diagnostics also supported the findings. The model based on a Chinese population in 2013 (model 3) showed the best and most stable predictive performance in all the tests and was more informative in CYP3A5 extensive metabolizers. As expected, Bayesian forecasting improved model predictability. Diversity among models and between different CYP3A5 genotypes of the same model was also narrowed by Bayesian forecasting.Conclusions: Based on our results, we recommend using model 3 in CYP3A5 extensive metabolizers in clinical practice. All models had a poor predictive performance in CYP3A5 poor metabolizers, and they should be used with caution in this patient population. However, Bayesian forecasting improved the predictability and reduced differences, and thus the models could be applied in this latter patient population for the design of maintenance dose. [ABSTRACT FROM AUTHOR]

Background and Objectives: Diltiazem is a benzothiazepine calcium blocker and widely used in renal transplant patients since it improves the level of tacrolimus or cyclosporine A concentration. Several population pharmacokinetic (PopPK) models had been established for cyclosporine A and tacrolimus but no specific PopPK model was established for diltiazem. The aim of the study is to develop a PopPK model for diltiazem in renal transplant recipients and provide relevant pharmacokinetic parameters of diltiazem for further pharmacokinetic interaction study.Methods: Patients received tacrolimus as primary immunosuppressant agent after renal transplant and started administration of diltiazem 90 mg twice daily on 5th day. The concentration of diltiazem at 0, 0.5, 1, 2, 8, and 12 h was measured by high-performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS). Genotyping for CYP3A4*1G, CYP3A5*3, and MDR1 3435 was conducted by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). 25 covariates were considered in the stepwise covariate model (SCM) building procedure.Results: One-compartment structural pharmacokinetic model with first-order absorption and elimination was used to describe the pharmacokinetic characteristics of diltiazem. Total bilirubin (TBIL) influenced apparent volume of distribution (V/F) of diltiazem in the forward selection. The absorption rate constant (Ka), V/F, and apparent oral clearance (CL/F) of the final population pharmacokinetic (PopPK) model of diltiazem were 1.96/h, 3550 L, and 92.4 L/h, respectively.Conclusion: A PopPK model of diltiazem is established in Chinese renal transplant recipients and it will provide relevant pharmacokinetic parameters of diltiazem for further pharmacokinetic interaction study. [ABSTRACT FROM AUTHOR]

Aim:To study the effects of delayed and missed doses (poor compliance) on the pharmacokinetics of carbamazepine (CBZ) and its main active metabolite carbamazepine-10,11-epoxide (CBZE) in Chinese epilepsy patients using Monte Carlo simulation.Methods:CBZ and CBZE time-concentration profiles in various scenarios were generated based on a population pharmacokinetic study in Chinese epilepsy patients using Monte Carlo simulation. The scenarios included patients given multiple doses of CBZ that ranged from 100 to 300 mg three times daily or from 200 to 300 mg every 12 h. The therapeutic range of CBZ and CBZE for each scenario was estimated to assess the effect of delayed or missed doses and to design corresponding rescue regimens. Moreover, the impact of body weight, absorption rate and co-therapy with other antiepileptic drugs (phenytoin, phenobarbital and valproic acid) on the dosage recommendation was investigated in the event of poor compliance.Results:The risk for a sub-therapeutic range of CBZ and CBZE was increased in a dose-dependent manner in both two and three times daily regimens when delayed or missed doses occurred. The effects of poor compliance was less prominent on the lower daily doses compared with those on the higher daily doses. The dose recommendations, in the event of poor compliance, were time related and dose dependent. Patient body weight, absorption rate and co-therapy with phenytoin, phenobarbital and valproic acid had no significant impact on the dose recommendation.Conclusion:Patients with epilepsy should take the delayed doses as soon as they remember, and partial missed doses may need to be taken near or at the next scheduled time. [ABSTRACT FROM AUTHOR]