Pharmacokinetic Parameters Of Drug Research Articles

Unlocking the Blood-Brain Barrier for Enhanced Curcumin Delivery Using PEGylated Mesoporous Silica Nanoparticles

The blood-brain barrier is a physiological barrier that regulates the entry of substances the brain. BBB poses a challenge for delivering drugs to brain. To address this challenge, a nano-system (P/CurMSNs) was fabricated. The study evaluated P/CurMSNs potential to cross blood brain barrier, via various administration routes; intraperitoneal, intranasal, and intravenous using mice model. The intranasal administration of P/CurMSNs exhibited the most efficient curcumin delivery to the brain in 30 min, achieving 366 ±37 ng/ml relative to 264 ±22 ng/ml and 303± 41 ng/ml for intraperitoneal and intravenous routes, respectively. Post intranasal administration, drug pharmacokinetic parameters were significantly higher in brain and lower in plasma and vital organs, when compared to the other administration routes. In conclusion, P/MSNs emerged as a promising strategy for delivering drug across blood brain barrier via the three routes, particularly intranasal administration, offering a potential therapeutic approach for brain disorders with enhanced brain tissue targeting.

In Vitro In Vivo Extrapolation and Bioequivalence Prediction for Immediate-Release Capsules of Cefadroxil Based on a Physiologically-Based Pharmacokinetic ACAT Model.

Physiologically based pharmacokinetic (PBPK) modeling is a mechanistic concept, which helps to judge the effects of biopharmceutical properties of drug product such as in vitro dissolution on its pharmacokinetic and in vivo performance. With the application of virtual bioequivalence (VBE) study, the drug product development using model-based approach can help in evaluating the possibility of extending BCS-based biowaiver. Therefore, the current study was intended to develop PBPK model as well as in vitro in vivo extrapolation (IVIVE) for BCS class III drug i.e. cefadroxil.A PBPK model was created in GastroPlus™ 9.8.3 utilizing clinical data of immediate-release cefadroxil formulations. By the examination of simulated and observed plasma drug concentration profiles, the predictability of the proposed model was assessed for the prediction errors. Furthermore, mechanistic deconvolution was used to create IVIVE, and the plasma drug concentration profiles and pharmacokinetic parameters were predicted for different virtual formulations with variable cefadroxil in vitro release. Virtual bioequivalence study was also executed to assess the bioequivalence of the generic verses the reference drug product (Duricef®).The developed PBPK model satisfactorily predicted Cmax and AUC0-t after cefadroxil single and multiple oral dose administrations, with all individual prediction errors within the limits except in a few cases. Second order polynomial correlation function obtained accurately predict in vivo drug release and plasma concentration profile of cefadroxil test and reference (Duricef®) formulation. The VBE study also proved test formulation bioequivalent to reference formulation and the statistical analysis on pharmacokinetic parameters reported 90% confidence interval for Cmax and AUC0-t in the FDA acceptable limits.The analysis found that a validated and verified PBPK model with a mechanistic background is as a suitable approach to accelerate generic drug development.

RAPID DISSOLUTION: DEVELOPMENT AND ASSESSMENT OF A NOVEL DRUG FORMULATION

This study focuses on the development and assessment of a novel fast-dissolving drug formulation aimed at improving drug delivery efficiency and patient compliance. The formulation was designed to dissolve rapidly in the oral cavity, facilitating quick absorption and onset of action. Through a systematic approach, the formulation's composition, including excipients and active pharmaceutical ingredients, was optimized to achieve rapid dissolution while maintaining stability and bioavailability. Various techniques, such as direct compression, freeze-drying, and spray drying, were explored to produce the fast-dissolving drug formulation. Evaluation of the formulation involved assessments of dissolution kinetics, drug release profile, physical characteristics, and pharmacokinetic parameters. The results demonstrate the potential of the fast-dissolving drug formulation to offer enhanced drug delivery and improved patient experience, making it a promising option for pharmaceutical development.

Studies on cationic ocular emulsions containing bipartitioned oil droplets to codeliver cyclosporin A and etodolac.

Background: To prepare ocular emulsions containing bipartitioned oil droplets to entrap cyclosporin A (0.05% w/w) and etodolac (0.2% w/w) by using castor, olive and silicon oils. Methods: The physicochemical characterizations of prepared emulsions were performed. The drug's biodistribution profiles and pharmacokinetic parameters from emulsions were checked using the ultraperformance liquid chromatography-tandemmass spectrometry method in the ocular tissues of the healthy rabbit eye model. Results: The emulsions displayed 365.13±7.21nm size and 26.45±2.09mV zeta potential. The ferrying of two drugs after releasing from emulsions occurred across corneal/conjunctival tissues to enter the vitreous and sclera following a single drop administration into the rabbit's eyes. Conclusion: The dual drug-loaded emulsions weremore likely to produce synergistic anti-inflammatory activity for managing moderate-to-severe dry eye disease.

The Synergistic Influence of Polyflavonoids from Citrus aurantifolia on Diabetes Treatment and Their Modulation of the PI3K/AKT/FOXO1 Signaling Pathways: Molecular Docking Analyses and In Vivo Investigations.

This study was aimed at probing the modulatory influence of polyflavonoids extracted from Citrus aurantifolia, lemon peel extract (LPE-polyflavonoids), on attenuating diabetes mellitus (DM) and its complications. HPLC investigations of the LPE exhibited the incidence of five flavonoids, including diosmin, biochanin A, hesperidin, quercetin, and hesperetin. The in silico impact on ligand-phosphatidylinositol 3-kinase (PI3K) interaction was investigated in terms of polyflavonoid class to explore the non-covalent intakes and binding affinity to the known protein active site. The drug likeness properties and pharmacokinetic parameters of the LPE-polyflavonoids were investigated to assess their bioavailability in relation to Myricetin as a control. Remarkably, the molecular docking studies demonstrated a prominent affinity score of all these agents together with PI3K, implying the potency of the extract to orchestrate PI3K, which is the predominant signal for lessening the level of blood glucose. To verify these findings, in vivo studies were conducted, utilizing diabetic male albino rats treated with LPE-polyflavonoids and other groups treated with hesperidin and diosmin as single flavonoids. Our findings demonstrated that the LPE-polyflavonoids significantly ameliorated the levels of glucose, insulin, glycogen, liver function, carbohydrate metabolizing enzymes, G6Pd, and AGEs compared to the diabetic rats and those exposed to hesperidin and diosmin. Furthermore, the LPE-polyflavonoids regulated the TBARS, GSH, CAT, TNF-α, IL-1β, IL-6, and AFP levels in the pancreatic and hepatic tissues, suggesting their antioxidant and anti-inflammatory properties. In addition, the pancreatic and hepatic GLUT4 and GLUT2 were noticeably increased in addition to the pancreatic p-AKT in the rats administered with the LPE-polyflavonoids compared to the other diabetic rats. Remarkably, the administration of LPE-polyflavonoids upregulated the expression of the pancreatic and hepatic PI3K, AMPK, and FOXO1 genes, emphasizing the efficiency of the LPE in orchestrating all the signaling pathways necessitated to reduce the diabetes mellitus. Notably, the histopathological examinations of the pancreatic and hepatic tissues corroborated the biochemical results. Altogether, our findings accentuated the potential therapeutic role of LPE-polyflavonoids in controlling diabetes mellitus.

Design of a Cyclodextrin Bioproduction Process Using Bacillus pseudofirmus and Paenibacillus macerans

Cyclodextrin (CD) drug delivery systems offer the potential to enhance the desired physicochemical properties and pharmacokinetic parameters of drugs while maintaining their safety. Cyclodextrin-glucosyl-transferase (CGTase) is amongst the most important enzymes used in CD biosynthesis. However, the bioproduction of CDs still faces challenges in terms of optimization and process complexity. This study proposes a novel CD bioproduction system in a batch mode to increase yield and reduce costs. Two bacterial strains were selected: the alkalophilic Bacillus pseudofirmus DSM2517 strain and the neutrophilic Paenibacillus macerans DSM1574 strain. Three different culture media, two temperatures (30 °C and 37 °C), and three scales (shake flasks 20 mL and 100 mL, and bioreactor 3.2 L) were evaluated with respect to bacterial growth kinetics, protein production, and CGTase biosynthesis and activity for β-CD production. Bacterial growth was monitored by measuring optical density (OD600 nm), while CGTase activity was assessed by measuring β-CD production directly in the medium after filtration or in samples after concentration (using a Vivaspin 500® ultrafiltration spin column with a 10 kDa cut-off). β-CD quantification was performed using the phenolphthalein colorimetric method and HPLC. The best conditions for combined growth and protein production, for both microorganisms, in shake flasks were achieved with a medium containing 2% dextrin as the carbohydrate source. Scale-up to the bioreactor displayed improved growth kinetics for both bacteria and higher protein production and CGTase activity for Paenibacillus macerans.

A Panoptic Review on Improvement in Chemothera-peutic Properties of Cytotoxic Drugs through Calixarene

Cancer is one of the most fatal and complicated diseases. Chemotherapeutic drugs occupy a crucial position in cancer treatment, although it is still challenging to cure it from the root cause without harming healthy cells. Adjuvant or neoadjuvant and concurrent chemotherapies are usually used along with surgery and radiotherapy, depending on the spreading of tumour cells to its vicinity. However, it cannot wholly kill cancerous cells, which further develop after a while; the reason behind this is poor drug pharmacokinetic and biopharmaceutical parameters. Considering the approach of calixarenes, it has significantly drawn attention that can lodge drug molecules by forming inclusion complexes due to their prominent geometrical shape distinguishing them from other heterocyclic compounds.
 Moreover, it can be more beneficial if used with nano carrier-based systems like liposomes, liposomes, nanoparticles, micelles, milliards, and siRNA to deliver anticytotoxic agents. This review highlights the potential of calixarenes properties and nanocarrier calixarene-complexed based molecules, which provide better therapeutic properties without harming healthy cells due to their unique targeted attribution. Thus, it can overcome the problem arising from conventional therapies.

Role of in vitro two-dimensional (2D) and three-dimensional (3D) cell culture systems for ADME-Tox screening in drug discovery and development: a comprehensive review.

Drug discovery and development have become a very time-consuming and expensive process. Preclinical animal models have become the gold standard for studying drug pharmacokinetic and toxicity parameters. However, the involvement of a huge number of animal subjects and inter-species pathophysiological variations between animals and humans has provoked a lot of debate, particularly because of ethical concerns. Although many efforts are being established by biotech and pharmaceutical companies for screening new chemical entities in vitro before preclinical trials, failures during clinical trials are still involved. Currently, a large number of two- dimensional (2D) in vitro assays have been developed and are being developed by researchers for the screening of compounds. Although these assays are helpful in screening a huge library of compounds and have shown perception, there is a significant lack in predicting human Absorption, Distribution, Metabolism, Excretion and Toxicology (ADME-Tox). As a result, these assays cannot completely replace animal models. The recent inventions in three-dimensional (3D) cell culture-based assays like organoids and micro-physiological systems have shown great potential alternative tools for predicting the compound pharmacokinetic and pharmacodynamic fate in humans. In this comprehensive review, we have summarized some of the most commonly used 2D in vitro assays and emphasized the achievements in next-generation 3D cell culture-based systems for predicting the compound ADME-Tox.

Part II : Statistics in practice: Study design and application of inferential statistics—Interventional research

Part <scp>II</scp> : Statistics in practice: Study design and application of inferential statistics—Interventional research

Prediction of CYP-mediated silybin A-losartan pharmacokineticinteractions using physiological based pharmacokinetic modeling.

The concomitant use of herbal products and synthetic drugs necessitates the assessment of their interaction potentials. The herbal hepatoprotective medicine, silybin A inhibits cytochrome P450 (CYP) 2C9 and 3A4 enzymes, thus, may interact with the drugs that are substrates of CYP2C9 and 3A4, such as losartan. The three most prominent genotypes, expressed by CYP2C9 are the CYP2C9*1/*1, CYP2C9*1/*2 and CYP2C9*1/*3. This study aimed to assess silybin A-losartan interaction in different CYP2C9 genotypes using physiological-based pharmacokinetic (PBPK) model approach. The individual PBPK models for silybin A and losartan were developed using PK-Sim®. Losartan pharmacokinetics was predicted with or without co-administration of silybin A in individuals of different CYP2C9 genotypes to find herbal-drug interaction. The predicted drug plasma curves and pharmacokinetic parameters were optimized using parameter identification tool and were compared with reported pharmacokinetic parameters from the published clinical studies for model validation. The silybin-losartan interactions were predicted by change in area under the curve (AUC) and peak systemic concentration (Cmax). The co-treatment of silybin A, 420mg/24h (140mg/8h) with losartan 50mg/24h, exhibited a genotype-dependent change in the losartan's AUC and Cmax. In CYP 2C9*1/*1 genotype, AUC and Cmax of losartan were increased 1.16 and 1.37 folds, respectively falling in a range stipulated for negligible interaction. Increase in AUC and Cmax by 0.873 and 0.294 folds, respectively in CYP2C9*1/*3 after co-administration of silybin A exhibited a minor interaction with losartan. However, in individuals with CYP2C9*1/*2 genotype, the losartan's AUC and Cmax were decreased by 0.01 folds, manifesting a moderate interaction. Hence, in CYP2C9*1/*1 and CYP2C9*1/*3 genotypes, silybin A is a weak CYP inhibitor for losartan while in CYP2C9*1/*2 genotype, the co-administration of silybin consequents into a moderate pharmacokinetic interaction with losartan.

Synthesis of novel combinatorial drug delivery system (nCDDS) for co-delivery of 5-Fluorouracil and Leucovorin calcium for colon targeting and controlled drug release

Objective: Purpose of the current study was to improve the oral effectiveness of 5-Fluorouracil (5-FU) by developing novel controlled, combinatorial drug delivery system (nCDDS) for co-delivery of 5-FU and Leucovorin (LC) for colon targeting. Significance: on the basis of results obtained, novel controlled, combinatorial drug delivery system (nCDDS) could be an effective strategy for the colon targeting of 5-FU and LC. Methods: Free radical polymerization method was tuned and used to fabricate this nCDDS. The nCDDS is synthesized in two steps, firstly synthesis of 5-fluoruracil/leucovorin calcium loaded nanogels and secondly, pre-synthesized 5-FU & LC loaded nanogels were dispersed in pectin based polymerized matrix hard gel. The nanogels and nCDD gels were characterized for network structure, thermal stability and surface morphology. Swelling and in-vitro release studies were carried out at different pH 1.2 and 7.4 both for naive nanogels and combined matrix gels. In-vivo study of combinatorial gel was performed on rabbits by using HPLC method to estimate plasma drug concentration and pharmacokinetics parameters. Results: Structure and thermal analysis confirmed the formation of stable polymeric network. SEM of nanogels and combinatorial gels showed that the spongy and rough edges particles and uniformly distributed in the combinatorial gel. The prepared nCDDS showed excellent water loving capacity and pH responsiveness. Combinatorial gel showed excellent characteristic for colonic delivery of drugs, which were confirmed by various in-vitro and in-vivo characterization. Acute oral toxicity study of combinatorial gel confirmed the biocompatible and non-toxic characteristics of developed formulation. Conclusion: Conclusively it can be found that nCDDS showed excellent properties regarding drug targeting in a controllable manner as compared to naive PEGylated nanogels.

Influence of Inflammation on Cytochromes P450 Activity in Adults: A Systematic Review of the Literature.

Background: Available in-vitro and animal studies indicate that inflammation impacts cytochromes P450 (CYP) activity via multiple and complex transcriptional and post-transcriptional mechanisms, depending on the specific CYP isoforms and the nature of inflammation mediators. It is essential to review the current published data on the impact of inflammation on CYP activities in adults to support drug individualization based on comorbidities and diseases in clinical practice. Methods: This systematic review was conducted in PubMed through 7th January 2021 looking for articles that investigated the consequences of inflammation on CYP activities in adults. Information on the source of inflammation, victim drugs (and CYPs involved), effect of disease-drug interaction, number of subjects, and study design were extracted. Results: The search strategy identified 218 studies and case reports that met our inclusion criteria. These articles were divided into fourteen different sources of inflammation (such as infection, autoimmune diseases, cancer, therapies with immunomodulator…). The impact of inflammation on CYP activities appeared to be isoform-specific and dependent on the nature and severity of the underlying disease causing the inflammation. Some of these drug-disease interactions had a significant influence on drug pharmacokinetic parameters and on clinical management. For example, clozapine levels doubled with signs of toxicity during infections and the concentration ratio between clopidogrel’s active metabolite and clopidogrel is 48-fold lower in critically ill patients. Infection and CYP3A were the most cited perpetrator of inflammation and the most studied CYP, respectively. Moreover, some data suggest that resolution of inflammation results in a return to baseline CYP activities. Conclusion: Convincing evidence shows that inflammation is a major factor to be taken into account in drug development and in clinical practice to avoid any efficacy or safety issues because inflammation modulates CYP activities and thus drug pharmacokinetics. The impact is different depending on the CYP isoform and the inflammatory disease considered. Moreover, resolution of inflammation appears to result in a normalization of CYP activity. However, some results are still equivocal and further investigations are thus needed.

An UPLC-MS/MS method to monitor Estriol injection and comparison of pharmacokinetic characteristics after irradiation

ObjectiveTo develop an UPLC-MS/MS method for the accurate quantification of Estriol (E3), a new radioprotective agent, and observe the variation in pharmacokinetic characteristics of E3 after irradiation. As a hormone drug, the gender differences of E3 metabolism were also concerned here. MethodsVarious chromatographic and mass spectrometric conditions of E3 were optimized. The specificity, linearity, precision and accuracy of UPLC-MS/MS method were validated. Twenty SD rats, half male and half female, were administered with intramuscular (im) injection of 2.7 ​mg/kg E3, and then divided randomly into two groups, sham-irradiated group (Con) and irradiated group (IR). IR group was irradiated to 7 ​Gy of γ-rays. Blood samples were collected at different times post-irradiation and E3 concentrations were detected. The changes of concentration-time variation and pharmacokinetic parameters for E3 after irradiation were investigated, together with metabolic differences between male and female rats. ResultsThe range of the calibration curve of UPLC-MS/MS for E3 was 1.00–200.0 ​ng/mL. Con group reached maximum concentration (Cmax) (77.57 ​± ​18.71) ng/mL at (0.68 ​± ​0.29) h (Tmax) after im injection. The drug concentration-time profiles and pharmacokinetic parameters of E3 were consistent before and after irradiation. The areas under time curve (AUC0-t) of E3 were (353 ​± ​74) h·ng/mL for Con group, and (299 ​± ​74) h·ng/mL for IR group (P ​> ​0.05). There were also no statistical differences in pharmacokinetic parameters between female and male rats. The elimination half-lifes (T1/2) of males and females were (3.02 ​± ​0.68) h and (3.01 ​± ​0.42) h in Con group, and (3.64 ​± ​0.51) h and (3.38 ​± ​0.60) h in IR group, respectively (P ​> ​0.05). ConclusionA rapid and sensitive UPLC-MS/MS method for determination of E3 was established. The pharmacokinetic characteristics of E3 in rat were not affected by 7 ​Gy irradiation and gender differences. This study provided a theoretical basis for the development and application of new radiation injury treatment drug.

Piperacillin-Tazobactam in Intensive Care Units: A Review of Population Pharmacokinetic Analyses.

Piperacillin-tazobactam is a potent β-lactam/β-lactamase inhibitor antibiotic commonly prescribed in the intensive care unit setting. Admitted patients often show large variability in treatment response due to multiple pathophysiological changes present in this population that alter the drug's pharmacokinetics. This review summarizes the population pharmacokinetic models developed for piperacillin-tazobactam and provides comprehensive data on current dosing strategies while identifying significant covariates in critically ill patients. A literature search on the PubMed database was conducted, from its inception to July 2020. Relevant articles were retained if they met the defined inclusion/exclusion criteria. A total of ten studies, published between 2009 and 2020, were eligible. One- and two-compartment models were used in two and eight studies, respectively. The lowest estimated piperacillin clearance value was 3.12 L/h, and the highest value was 19.9 L/h. The estimations for volume of distribution varied between 11.2 and 41.2 L. Tazobactam clearance values ranged between 5.1 and 6.78 L/h, and tazobactam volume of distribution values ranged between 17.5 and 76.1 L. The most frequent covariates were creatinine clearance and body weight, each present in four studies. Almost all studies used an exponential approach for the interindividual variability. The highest variability was observed in piperacillin central volume of distribution, at a value of 75.0%. Simulations showed that continuous or extended infusion methods performed better than intermittent administration to achieve appropriate pharmacodynamic targets. This review synthesizes important pharmacokinetic elements for piperacillin-tazobactam in an intensive care unit setting. This will help clinicians better understand changes in the drug's pharmacokinetic parameters in this specific population.

Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview.

The availability of long-acting injectable (LAI) antipsychotics for the treatment of schizophrenia provides clinicians with options that deliver continuous drug exposure and may improve adherence compared with daily oral antipsychotics. However, all LAI antipsychotics have unique formulations and pharmacokinetic characteristics that have implications for medication selection, administration interval, and injection site. This review outlines key differences in drug formulations and pharmacokinetics among LAI antipsychotics. A systematic search of the PubMed database was conducted to identify physical and formulation properties and pharmacokinetic data of commercially available LAI antipsychotics, including flupentixol decanoate, fluphenazine decanoate, haloperidol decanoate, zuclopenthixol decanoate, aripiprazole monohydrate, aripiprazole lauroxil, olanzapine pamoate, paliperidone palmitate, risperidone microspheres, and risperidone polymeric microspheres. Additional information was obtained from package inserts and product monographs. Relevant data on drug properties, administration details, pharmacokinetic parameters, and oral dose equivalencies of LAI antipsychotics are summarized. Based on our analysis, formulation characteristics (e.g., vehicle medium) and administration characteristics (e.g., injection site) can affect rate of absorption and adverse effects and may factor into whether oral supplementation or an additional injection is needed. Dose adjustments may be necessary based on potential drug–drug interactions, and approximate dose equivalence with oral formulations can help inform titration when switching from oral to LAI formulations. Clinicians administering LAI antipsychotics should consider these formulation and pharmacokinetic factors to maximize clinical impact and to adjust to an individual patient’s needs and treatment goals.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40263-020-00779-5.

Comparative Study of the Pharmacokinetics and Bioequivalence of Meldonium and Mildronate® Preparations

Acomparative study of the pharmacokinetics, bioequivalence, and safety of two marketed meldonium dosage forms Meldonium Organika (meldonium, 500 mg capsules, Organika Co., Russia) and Mildronate® (meldonium, 500 mg capsules, Grindex Co., Latvia) was carried out for a group of healthy volunteers in an open randomized 2-period cross-validation test. It was established that 90% confidence intervals for the ratio of geometric means of pharmacokinetic parameters AUC0-t (86.32 – 102.48%), AUC0-∞ (85.30 – 101.68%), and Cmax (84.92 – 101.76%) did not go beyond permissible limits of 80.00 – 125.00%. A conclusion was made about the bioequivalence of the aforementioned meldonium preparations based on the drug pharmacokinetic parameters.

Equine Drug Transporters: A Mini-Review and Veterinary Perspective.

Xenobiotic transport proteins play an important role in determining drug disposition and pharmacokinetics. Our understanding of the role of these important proteins in humans and pre-clinical animal species has increased substantially over the past few decades, and has had an important impact on human medicine; however, veterinary medicine has not benefitted from the same quantity of research into drug transporters in species of veterinary interest. Differences in transporter expression cause difficulties in extrapolation of drug pharmacokinetic parameters between species, and lack of knowledge of species-specific transporter distribution and function can lead to drug–drug interactions and adverse effects. Horses are one species in which little is known about drug transport and transporter protein expression. The purpose of this mini-review is to stimulate interest in equine drug transport proteins and comparative transporter physiology.

A Review of Current Methods for Food Effect Prediction During Drug Development

Ingestion of oral dosage forms with food can drastically change drug pharmacokinetic parameters to consumption in fasted state. Accurate prediction of food effect (FE) is an important focus during drug development, as well as a requirement for drug approval by the Food and Drug Administration. FE can significantly restrict the clinical usefulness of drugs and is a principal parameter that must be considered early in drug development. Several approaches are available to predict FE in the human, including cell culture models, a variety of small and large animal models, and, more recently, physiologically based pharmacokinetic computerized models that incorporate biorelevant drug physicochemical properties. Each has its own advantages and disadvantages. While many methods are available to study FE, not all of these methods are applicable, efficient, consistent, financially feasible, or reasonable for every drug or drug formulation. Most importantly, different models may offer different applicability in accurately predicting FE in human species. Drug development is a long and often expensive process. Understanding of and access to an appropriate, reproducible, frugal means of FE assessment is vital in the field of drug development in order to ensure the development of a safe and effective drug. The following review delineates the advantages and disadvantages of a variety of preclinical FE study methods. While no single approach is good enough to give completely reliable predictions, a combination of in vitro, in vivo, and in silico approach may be advantageous to predict FE.

In Silico Prediction of Intestinal Permeability by Hierarchical Support Vector Regression.

The vast majority of marketed drugs are orally administrated. As such, drug absorption is one of the important drug metabolism and pharmacokinetics parameters that should be assessed in the process of drug discovery and development. A nonlinear quantitative structure–activity relationship (QSAR) model was constructed in this investigation using the novel machine learning-based hierarchical support vector regression (HSVR) scheme to render the extremely complicated relationships between descriptors and intestinal permeability that can take place through various passive diffusion and carrier-mediated active transport routes. The predictions by HSVR were found to be in good agreement with the observed values for the molecules in the training set (n = 53, r2 = 0.93, = 0.84, RMSE = 0.17, s = 0.08), test set (n = 13, q2 = 0.75–0.89, RMSE = 0.26, s = 0.14), and even outlier set (n = 8, q2 = 0.78–0.92, RMSE = 0.19, s = 0.09). The built HSVR model consistently met the most stringent criteria when subjected to various statistical assessments. A mock test also assured the predictivity of HSVR. Consequently, this HSVR model can be adopted to facilitate drug discovery and development.

AN OVERVIEW OF DRUG INFORMATION CENTER – FUNCTIONS AND CHALLENGES IN INDIA

Drug information has been providing data on drugs that are being used in the health-care system. It also bears dosing, adverse drug reactions (ADRs), side effects, pharmacokinetic parameters and educating the health-care professionals and managing drug shortage, identifying alternative treatments, and developing alternative protocols for restrictive use. The Moto of drug information is to contribute genuine, precise, appropriate, impartial drug information to the patients, nursing staff, practicing physician, pharmacist, and other health-care professional. Drug information regularly responds to inquiries from patients, health-care professionals. The drug information center routinely receives queries from hospital staff, patients, and responds to queries regarding ADRs, drug interactions, pharmacokinetic parameters of drugs, and information on new drugs available in the market. Drug information services help in improving patient safety, minimizing drug-related issues to the patient, and rational use of drugs by both physician and patient. Drug information services are providing unambiguous data with a well-trained and registered clinical pharmacist. Most of the developed countries are using this service successfully. In well-developed countries, these centers provide accurate and up to date drug information to health-care professionals within minutes. However, developing countries like India need to pay more attention to the services. Information present in this paper not only enlightens the drug information services but also on the future aspects that need to be taken.