Accurate Density Prediction of Sesquiterpenoid HEDFs and the Multiproperty Computing Server SesquiterPre.

Accurate and rapid evaluation of density is crucial for evaluating the packing and combustion characteristics of high-energy-density fuels (HEDFs). This parameter is pivotal in the selection of high-performance HEDFs. Our study leveraged a polycyclic compound density data set and quantum chemical (QC) descriptors to establish a correlation with the target properties using the XGBoost algorithm.

Long-term prognosis of patients with gallbladder carcinoma after curative-intent resection based on changes in the ratio of carbohydrate antigen 19-9 to total bilirubin (CA19-9/TB): a multicenter retrospective cohort study.

Background: The prognostic value of carbohydrate antigen 19-9 (CA19-9) is known to be affected by elevated bilirubin levels in patients with gallbladder carcinoma (GBC). The clinical significance of changes in the ratio of CA19-9 levels to total bilirubin (TB) levels in patients with GBC after curative-intent resection remains unknown. The aim of this study was to determine the prognostic value of changes in preoperative and postoperative CA19-9/TB ratio in these patients.

External evaluation of published population pharmacokinetic models of polymyxin B.

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.

Quantitative structure-toxicity relationship model for acute toxicity of organophosphates via multiple administration routes in rats and mice.

Organophosphates (OPs) are highly toxic compounds, with widespread application in agricultural and chemical industries, whose introduction into the environment poses serious hazards to humans and ecological systems. To assess and ultimately mitigate these hazards, this study predicted the acute toxicity of OPs according to their chemical structure and administration route. The acute toxicity data of 161 OPs in two species via six different administration routes were manually collected and used to develop a series of quantitative structure-toxicity relationship (QSTR) models with robust and practical predictive abilities.

Remedial dosing recommendations for delayed or missed doses of valproic acid in patients with epilepsy based on Monte Carlo simulations.

Objective: Delayed or missed doses are unavoidable in the pharmacotherapy of epilepsy and significantly compromise the efficacy of antiepileptic drug treatment. An inappropriate remedial regimen can cause seizure relapse or serious adverse events. This study investigated the effect of delayed or missed doses on the pharmacokinetics (PK) of valproic acid (VPA) in patients with epilepsy and established remedial dosing recommendations for nonadherent patients.

Improving Docking-Based Virtual Screening Ability by Integrating Multiple Energy Auxiliary Terms from Molecular Docking Scoring.

Virtual Screening (VS) based on molecular docking is an efficient method used for retrieving novel hit compounds in drug discovery. However, the accuracy of the current docking scoring function (SF) is usually insufficient. In this study, in order to improve the screening power of SF, a novel approach named EAT-Score was proposed by directly utilizing the energy auxiliary terms (EAT) provided by molecular docking scoring through eXtreme Gradient Boosting (XGBoost).

How to Handle Delayed or Missed Doses: A Population Pharmacokinetic Perspective.

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.

Structural Analysis and Identification of Colloidal Aggregators in Drug Discovery.

Aggregation has been posing a great challenge in drug discovery. Current computational approaches aiming to filter out aggregated molecules based on their similarity to known aggregators, such as Aggregator Advisor, have low prediction accuracy, and therefore development of reliable in silico models to detect aggregators is highly desirable. In this study, we built a data set consisting of 12 119 aggregators and 24 172 drugs or drug candidates and then developed a group of classification models based on the combination of two ensemble learning approaches and five types of molecular representations.

Remedial dosing recommendations for delayed or missed doses of lamotrigine in pediatric patients with epilepsy using Monte Carlo simulations.

Objective: This study investigated the effect of delayed or missed doses on the pharmacokinetics (PK) of lamotrigine (LTG) in children with epilepsy and established remedial dosing recommendations for nonadherent patients.

Methods: The Monte Carlo simulation based on a published LTG population PK model was used to assess the effect of different scenarios of nonadherence and the subsequently administered remedial regimens. The following three remedial approaches were investigated for each delayed dose: A) A partial dose was administered immediately, and the regular dose was administered at the next scheduled time.

Evaluating tacrolimus pharmacokinetic models in adult renal transplant recipients with different CYP3A5 genotypes.

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.

Population Pharmacokinetic Modeling of Diltiazem in Chinese Renal Transplant Recipients.

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.

Influences of CYP2D610 polymorphisms on the pharmacokinetics of iloperidone and its metabolites in Chinese patients with schizophrenia: a population pharmacokinetic analysis.

Aim: Iloperidone is an atypical antipsychotic drug that is mainly metabolized by CYP2D6, CYP3A4, and cytosolic enzymes. Previous studies show that extensive and poor metabolizers of CYP2D6 exhibit different plasma concentrations of iloperidone and its metabolites. The aim of this study was to develop a parent-metabolite population pharmacokinetic (PPK) model to quantify the effects of CYP2D610 allele on the pharmacokinetics of iloperidone and its metabolites in Chinese schizophrenia patients.

[Effects of multiple-trough sampling design and algorithm on the estimation of population and individual pharmacokinetic parameters].

The purpose of this study is to investigate the effects of multiple-trough sampling design and nonlinear mixed effect modeling (NONMEM) algorithm on the estimation of population and individual pharmacokinetic parameters. Oxcarbazepine and tacrolimus were used as one-compartment and two-compartment model drugs, respectively. Seven sampling designs were investigated using various number of trough concentrations per individual ranging from 1-4.

Psychiatric illness and intellectual disability in the Prader-Willi syndrome with different molecular defects--a meta analysis.

Background And Objectives: Several studies have suggested a difference in clinical features of intellectual ability and psychiatric illness in the Prader-Willi syndrome (PWS) with the 15q11-q13 paternal deletion and maternal uniparental disomy (mUPD). Our objective was to appraise evidence on this association through a meta-analysis.

Methods: The electronic records PubMed and EMBASE from 1956 to 2012 were extracted for meta-analysis.

Effects of CYP3A4 and CYP3A5 polymorphisms on tacrolimus pharmacokinetics in Chinese adult renal transplant recipients: a population pharmacokinetic analysis.

Objective: Tacrolimus is used clinically for the long-term treatment of antirejection of transplanted organs in liver and kidney transplant recipients, although dose optimization is poorly managed. The aim of this study was to examine the association between tacrolimus pharmacokinetic variability and CYP3A4 and CYP3A5 genotypes by a population pharmacokinetic analysis based on routine drug monitoring data in adult renal transplant recipients.

Materials And Methods: Trough tacrolimus concentrations were obtained from 161 adult kidney transplant recipients after transplantation.

The effect of poor compliance on the pharmacokinetics of carbamazepine and its epoxide metabolite using Monte Carlo simulation.

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.

[Estimation of individual pharmacokinetic parameters using maximum a posteriori Bayesian method with D-optimal sampling strategy].

This study was aimed to develop a maximum a posteriori Bayesian (MAPB) estimation method to estimate individual pharmacokinetic parameters based on D-optimal sampling strategy. Meanwhile, the performance of MAPB was compared with the multiple linear regression (MLR) method in terms of accuracy and precision. Pharmacokinetic study of pioglitazone was employed as the example case.

The association of the UGT1A8, SLCO1B3 and ABCC2/ABCG2 genetic polymorphisms with the pharmacokinetics of mycophenolic acid and its phenolic glucuronide metabolite in Chinese individuals.

Background: This study aimed to evaluate the effect of UGT1A8*2, SLCO1B3 T334G, ABCC2 C-24T and ABCG2 C421A polymorphisms on the pharmacokinetics (PKs) of mycophenolic acid (MPA) and its phenolic glucuronide (MPAG) in healthy Chinese volunteers and in stable renal transplant patients.

Methods: The data were extracted from comparative bioavailability studies conducted in 42 healthy individuals and 37 renal transplant patients. A complete PK profile was obtained over 48 h for healthy volunteers and over 12h for the transplant patients.

Population pharmacokinetic modelling for enterohepatic circulation of mycophenolic acid in healthy Chinese and the influence of polymorphisms in UGT1A9.

What Is Already Known About This Subject: Mycophenolic acid (MPA) undergoes enterohepatic circulation (EHC) in the body and several population models have been proposed to describe this process using sparse data. Recent studies in Whites have found that polymorphism in UGT1A9 could partly explain the large interindividual variability associated with the pharmacokinetics of MPA.

What This Study Adds: A new population pharmacokinetic model for EHC combining MPA and its main glucuronide metabolite (MPAG) simultaneously was established based on physiological aspects of biliary excretion using intensive sampling data.

[Development and identifiability analysis of parent-metabolite pharmacokinetic model for risperidone and its main active metabolite 9-hydroxyrisperidone].

To develop a parent-metabolite pharmacokinetic model for risperidone (RIP) and its major active metabolite (9-hydroxyrisperidone) and investigate their pharmacokinetics characteristics in healthy male volunteers, twenty-two healthy volunteers were orally given a single dose of 2 mg RIP. Plasma samples were collected in the period of 96 hours and concentrations of RIP and 9-hydroxyrisperidone were measured by a validated HPLC/MS method. CYP2D6 phenotypes were identified by the T1/2 of RIP and 9-hydroxyrisperidone according to the literature.

[Bioequivalence assessment of pioglitazone hydrochloride oral preparation by limited sampling strategy].

Aim: To develop limited sampling strategy (LSS) for estimation of C(max) and AUC(0-t) and assessing the bioequivalence of two pioglitazone hydrochloride (PGT) preparations.

Methods: Healthy subjects (n = 20), enrolled in a bioequivalence study, were received 30 mg PGT po of reference or test formulation. The plasma concentration of PGT was determined by the validated HPLC method.

[New 3D amino acid structure descriptors and its application to the polypeptide QSAR].

Aim: To establish a new amino acid structure descriptor that can be applied to polypeptide QSAR studies.

Methods: The new amino acid structure descriptor c-scales were derived from a principal components analysis of 167 amino acid structure descriptor indexes by theoretic calculation. The c1,c2,c3-scales were related to 3D structural features of amino acid such as steric, electronic and conformation properties etc.

[Effect of MDR1 polymorphic expression on oral disposition of cyclosporine A].

Aim: To determine the relationship between C3435T mutation in exon 26 of the human multidrug resistant 1 gene and cyclosporine (CsA) pharmacokinetic (PK) parameters among healthy Chinese volunteers by nonlinear mixed effect model (NONMEM).

Methods: Twenty healthy subjects were given orally a single dose of 500 mg CsA in microemulsion solution. Blood CsA concentrations were measured with HPLC and the genotype for the C3435T polymorphism of MDR1 gene was determined with the PCR and restriction fragment length polymorphism.