Drug Absorption Studies Research Articles

Modulating nanostructures with polyvinylpyrrolidone: Design and development of a porous, biocompatible, and pH-Stable core-shell magnetic microrobot for demonstrating drug absorption from wastewater

Increased antineoplastic drug concentrations in wastewater stem from ineffective treatment plants and increased usage. Although microrobots are promising for pollutant removal, they face hurdles in developing a superstructure with superior adsorption capabilities, biocompatibility, porosity, and pH stability. This study focused on adjusting the PVP concentration from 0.05 to 0.375 mM during synthesis to create a favorable CMOC structure for drug absorption. Lower PVP concentrations (0.05 mM) yielded a three-dimensional nanoflower structure of CaMoO4 and CuS nanostructures, whereas five-fold concentrations (0.25 mM) produced a porous structure with a dense CuS core encased in a transparent CaMoO4 shell. The magnetically movable and pH-stable COF@CMOC microrobot, achieved by attaching CMOC to cobalt ferrite (CoF) NPs, captured doxorubicin efficiently, with up to 57 % efficiency at 200 ng/mL concentration for 30 min, facilitated by electrostatic interaction, hydrogen bonding, and pore filling of DOX. The results demonstrated that DOX removal through magnetic motion showed superior performance, with an estimated improvement of 57% compared to stirring conditions (17 %). A prototype PDMS microchannel system was developed to study drug absorption and microrobot recovery. The CaMoO4 shell of the microrobots exhibited remarkable robustness, ensuring long-lasting functionality in harsh wastewater environments and improving biocompatibility while safeguarding the CuS core from degradation. Therefore, microrobots are a promising eco-friendly solution for drug extraction. These microrobots show promise for the selective removal of doxorubicin from contaminated wastewater.

Pharmacokinetics of cycloheximide in rats and evaluation of its effect as a blocker of intestinal lymph formation

Cycloheximide (CHX) has been used to reduce the flow of intestinal lymph and as a non-surgical tool to study drug absorption via the intestinal lymphatics. Pharmacokinetic information on the agent, and its relationship to effect and toxicity, have not been examined. The goal of this study was to provide pharmacokinetic data and link it to lymph-blocking and toxicological effects. Jugular-vein cannulated (JVC) adult Sprague-Dawley male rats were administered 0.5 mg/kg CHX by oral, intraperitoneal (ip), and intravenous routes followed by blood draws, and CHX was assayed using LC-MS/MS. Another four JVC rats were given peanut oil (2 mL/kg) without and then with CHX to measure effects on lipid absorption as a surrogate indicator of lymph flow. One-week later plasma biochemistry measures were obtained. The results indicated that CHX had a high clearance and volume of distribution, and oral absolute bioavailability of 0.47 with 0.5 mg/kg. CHX was associated with dose- and route-dependent pharmacokinetics. The relative bioavailability after ip doses was over 3. CHX had low plasma protein binding and minor urinary excretion. Metabolism appeared to be occur by oxidation and glucuronidation. Reductions in plasma lipids (24–40 %) were seen after 2.5 mg/kg orally with signs of inflammation and increased liver enzymes persisting for a week after the dose. CHX was associated with a reduction in lipid absorption after oral doses of 2.5 mg/kg, which seems to justify its use as a non-surgical tool to evaluate the lymphatic pathway of absorption of drugs. However, it also possesses hepatotoxicity, which should be taken into consideration in its use.

The Path from Nasal Tissue to Nasal Mucosa on Chip: Part 1-Establishing a Nasal In Vitro Model for Drug Delivery Testing Based on a Novel Cell Line.

In recent years, there has been a significant increase in the registration of drugs for nasal application with systemic effects. Previous preclinical in vitro test systems for transmucosal drug absorption studies have mostly been based on primary cells or on tumor cell lines such as RPMI 2650, but both approaches have disadvantages. Therefore, the aim of this study was to establish and characterize a novel immortalized nasal epithelial cell line as the basis for an improved 3D cell culture model of the nasal mucosa. First, porcine primary cells were isolated and transfected. The P1 cell line obtained from this process was characterized in terms of its expression of tissue-specific properties, namely, mucus expression, cilia formation, and epithelial barrier formation. Using air-liquid interface cultivation, it was possible to achieve both high mucus formation and the development of functional cilia. Epithelial integrity was expressed as both transepithelial electrical resistance and mucosal permeability, which was determined for sodium fluorescein, rhodamine B, and FITC-dextran 4000. We noted a high comparability of the novel cell culture model with native excised nasal mucosa in terms of these measures. Thus, this novel cell line seems to offer a promising approach for developing 3D nasal mucosa tissues that exhibit favorable characteristics to be used as an in vitro system for testing drug delivery systems.

A novel physiologically based pharmacokinetic model of rectal absorption, evaluated and verified using clinical data on 10 rectally administered drugs

We present a physiologically based pharmacokinetic (PBPK) model simulating systemic drug concentrations following administration to the human rectum. Rectum physiology is parameterized based on literature data. The model utilizes in vitro release (IVRT) profiles from which drug mass transfer through the rectal fluid and tissue and into the systemic circulation are predicted. Due to a lack of data, rectal fluid and tissue absorption parameters are predicted either from colon absorption, with modifications relevant to rectal physiology, or optimized. The PBPK model is evaluated by simulating 29 clinical studies for 10 drugs. For 8 drugs (diazepam, diclofenac, indomethacin, naproxen, paracetamol, pentobarbital, phenobarbital and theophylline) the bias (average fold error, AFE) and precision (absolute average fold error, AAFE) of Cmax, AUC0-t and AUC0-inf simulations range from 0.87 to 2.22, indicating good agreement with observed values. For prochlorperazine and promethazine, the AFEs and AAFEs of Cmax predictions are 1.30 and 2.52, respectively. TheAUC0-t and AUC0-inf are overpredicted for both compounds(AFEs and AAFEs from 2.66 to 4.90). This results from a lack of reliable elimination data for prochlorperazine and the relevance of the IVRT profiles used in the promethazine model. The model paves the way for more mechanistic rectal drug absorption studies and virtual bioequivalence methods for rectal drug products.

Application of Machine Learning Technology in the Prediction of ADME- Related Pharmacokinetic Parameters.

As an important determinant in drug discovery, the accurate analysis and acquisition of pharmacokinetic parameters are very important for the clinical application of drugs. At present, the research and development of new drugs mainly obtain their pharmacokinetic parameters through data analysis, physiological model construction and other methods, but the results are often quite different from the actual situation, needing more manpower and material resources. We mainly discuss the application of machine learning technology in the prediction of pharmacokinetic parameters, which are mainly related to the quantitative study of drug absorption, distribution, metabolism and excretion in the human body, such as bioavailability, clearance, apparent volume of distribution and so on. This paper first introduces the pharmacokinetic parameters, the relationship between the quantitative structure-activity relationship model and machine learning, then discusses the application of machine learning technology in different prediction models, and finally discusses the limitations, prospects and future development of the machine learning model in predicting pharmacokinetic parameters. Unlike traditional pharmacokinetic analysis, machine learning technology can use computers and algorithms to speed up the acquisition of pharmacokinetic parameters to varying degrees. It provides a new idea to speed up and shorten the cycle of drug development, and has been successfully applied in drug design and development. The use of machine learning technology has great potential in predicting pharmacokinetic parameters. It also provides more choices and opportunities for the design and development of clinical drugs in the future.

285 Genetic Variation in the SLC22A1-3 Genes Influence the Risk of Congenital Anomalies

OBJECTIVES/GOALS: Congenital anomalies (CA) are common, but the cause is often unknown. The interplay between known environmental teratogens, such as medication use in pregnancy, and genetic predisposition impacts CA risk, but such interactions are poorly understood. We test the hypothesis that pharmacogenomic (PGx) variation impacts CA risk. METHODS/STUDY POPULATION: We performed a drug absorption, distribution, metabolism, and excretion (ADME) gene-wide association study (GWAS), which tests for a possible association between ADME gene single nucleotide polymorphisms and individuals with CAs. This analysis was performed in BioVU and utilized billing codes to identify 5,845 cases, individuals with at least one CA, and 50,059 controls of genetically European ancestry. Using Plink software we analyzed 5,398 SNPs in 292 ADME genes across cases and controls. Results from this analysis drove us to further investigate the association between CA risk and SLC22A1-3. Next, we performed PrediXcan analyses to estimate the association between genetically predicted gene expression (GPGE) of SLC22A1-3 genes across all available tissues in the GTEx resource and CA risk. RESULTS/ANTICIPATED RESULTS: The ADME GWAS identified multiple variants on chromosome 6 in the region of SCL22A1-3 that were associated with the risk for CAs. The most significant variants were rs2048327, rs2292334, rs3088442, rs1810126, rs376563, and rs7758229, p DISCUSSION/SIGNIFICANCE: The combination of the known crucial pharmacological roles of OCT1-3 and the results of our ADME GWAS / PrediXcan analyses demonstrates that PGx burden, specifically variation in the SLC22A1-3 genes, influences the risk of developing CAs. This new understanding has the potential to personalize care for pregnant individuals to reduce the risk of CAs.

Using innovative tools for in vitro absorption, distribution, metabolism and excretion studies to efficiently and effectively support drug development.

Drug development is a complicated and lengthy process requiring a significant amount of intellectual and capital input, as well as extensive collaborations among various organizations and institutions. Contract research organizations play important roles at some or even all stages of the drug development process. To provide better service in in vitro drug absorption, disposition, metabolism and excretion studies, maintain data accuracy and promote work efficiency, we developed an integrated information system termed the 'Drug Metabolism Information System', and it is being used routinely by our drug metabolism department. The Drug Metabolism Information System assists scientists with assay design, data analysis and report drafting and thus reduces human error.

The Adaptation of the QV600 LLI Milli-Fluidics System to House Ex Vivo Gastrointestinal Tissue Suitable for Drug Absorption and Permeation Studies, Utilizing MALDI MSI and LC-MS/MS.

Careful formulation of pharmaceuticals for oral delivery is essential to ensure that the optimal amount of the active ingredient reaches its intended site of action. This chapter demonstrates how mass spectrometry can be used in conjunction with ex vivo tissue and an adapted milli-fluidics system to carry out a drug absorption study. MALDI MSI is used to visualize the drug within the small intestine tissue from the absorption experimentation. LC-MS/MS is used to complete a mass balance of the experiment and quantify the amount of drug that has permeated through the tissue.

Interaction of polymers with bile salts – Impact on solubilisation and absorption of poorly water-soluble drugs

Formulating poorly soluble drugs with polymers in the form of solid dispersions has been widely used for improving drug dissolution. Endogenous surface-active species present in the gut, such as bile salts, lecithin and other phospholipids, have been shown to play a key role in facilitating lipids and poorly soluble drugs solubilisation in the gut. In this study, we examined the possible occurrence of interactions between a model bile salt, sodium taurocholate (NaTC), and model spray dried solid dispersions comprising piroxicam and Hydroxypropyl Methylcellulose (HPMC), a commonly used hydrophilic polymer for solid dispersion preparation. Solubility measurements revealed the good solubilisation effect of NaTC on the crystalline drug, which was enhanced by the addition of HPMC, and further boosted by the drug formulation into solid dispersion. The colloidal behaviour of the solid dispersions upon dissolution in biorelevant media, with and without NaTC, revealed the formation of NaTC-HPMC complexes and other mixed colloidal species. Cellular level drug absorption studies obtained using Caco-2 monolayers confirmed that the combination of drug being delivered by solid dispersion and the presence of bile salt and lecithin significantly contributed to the improved drug absorption. Together with the role of NaTC-HPMC complexes in assisting the drug solubilisation, our results also highlight the complex interplay between bile salts, excipients and drug absorption.

A method of isolating and analysing drugs from cancer cells for preclinical research

The presented paper describes a new isolation method of recovery and analysis of selected drugs developed for preclinical research.The method uses the RP-HPLC technique (in a single chromatographic separation) and serves the recovery and analysis of selected drugs from neoplastic cells. It enables the determination of cytostatics statins, fibrates, and pioglitazone. Chromatographic separations of the tested compounds were carried out on a Gemini-NX 5 µ C18 (4.6 × 150 mm i.d.) column, in a gradient system with a mobile phase consisting of ACN (0.1% TFA) and water (0.1% TFA) at ambient temperature. The separations were carried out at a flow of 1 ml/min and UV detection of 220 nm. The inter-day and intra-day precision and accuracy of the method were determined. Extending the extraction time at reduced temperature resulted in a significant increase in the recovery of the pharmaceuticals in comparison with traditional extraction methods.The presence of the tested pharmaceuticals at defined retention times was confirmed by mass spectrometry. A recovery procedure for the tested compounds from biological material (medium, cell pellets) was developed at a level ranging between 93 and 99%. The utility of the new HPLC method has been confirmed in drug absorption studies as screening tests for the analysis of the new therapeutic compositions on melanoma cell lines.

Establishment and Characterization of Novel Human Intestinal In Vitro Models for Absorption and First-Pass Metabolism Studies.

Commonly used intestinal in vitro models are limited in their potential to predict oral drug absorption. They either lack the capability to form a tight cellular monolayer mimicking the intestinal epithelial barrier or the expression of cytochrome P450 3A4 (CYP3A4). The aim of this study was to establish a platform of colorectal cancer patient-derived cell lines for evaluation of human intestinal drug absorption and metabolism. We characterized ten 2D cell lines out of our collection with confluent outgrowth and long-lasting barrier forming potential as well as suitability for high throughput applications with special emphasis on expression and inducibility of CYP3A4. By assessment of the transepithelial electrical resistance (TEER) the cells barrier function capacity can be quantified. Very high TEER levels were detected for HROC60. A high basal CYP3A4 expression and function was found for HROC32. Eight cell lines showed higher CYP3A4 induction by stimulation via the vitamin D receptor compared to Caco-2 cells (5.1- to 16.8-fold change). Stimulation of the pregnane X receptor led to higher CYP3A4 induction in two cell lines. In sum, we identified the two cell lines HROC183 T0 M2 and HROC217 T1 M2 as useful tools for in vitro drug absorption studies. Due to their high TEER values and inducibility by drug receptor ligands, they may be superior to Caco-2 cells to analyze oral drug absorption and intestinal drug–drug interactions. Significance statement: Selecting appropriate candidates is important in preclinical drug development. Therefore, cell models to predict absorption from the human intestine are of the utmost importance. This study revealed that the human cell lines HROC183 T0 M2 and HROC217 T1 M2 may be better suited models and possess higher predictive power of pregnane X receptor- and vitamin D-mediated drug metabolism than Caco-2 cells. Consequently, they represent useful tools for predicting intestinal absorption and simultaneously enable assessment of membrane permeability and first-pass metabolism.

A proof of concept using the Ussing chamber methodology to study pediatric intestinal drug transport and age-dependent differences in absorption.

Little is known about the impact of age on the processes governing human intestinal drug absorption. The Ussing chamber is a system to study drug transport across tissue barriers, but it has not been used to study drug absorption processes in children. This study aimed to explore the feasibility of the Ussing chamber methodology to assess pediatric intestinal drug absorption. Furthermore, differences between intestinal drug transport processes of children and adults were explored as well as the possible impact of age. Fresh terminal ileal leftover tissues from both children and adults were collected during surgery and prepared for Ussing chamber experiments. Paracellular (enalaprilat), transcellular (propranolol), and carrier‐mediated drug transport by MDR1 (talinolol) and BCRP (rosuvastatin) were determined with the Ussing chamber methodology. We calculated apparent permeability coefficients and efflux ratios and explored their relationship with postnatal age. The success rate for the Ussing chamber experiments, as determined by electrophysiological measurements, was similar between children (58%, N = 15, median age: 44 weeks; range 8 weeks to 17 years) and adults (67%, N = 13). Mean serosal to mucosal transport of talinolol by MDR1 and rosuvastatin by BCRP was higher in adult than in pediatric tissues (p = 0.0005 and p = 0.0091). In contrast, within our pediatric cohort, there was no clear correlation for efflux transport across different ages. In conclusion, the Ussing chamber is a suitable model to explore pediatric intestinal drug absorption and can be used to further elucidate ontogeny of individual intestinal pharmacokinetic processes like drug metabolism and transport.

Crosslinked and biofunctionalized γ-cyclodextrin metal organic framework to enhance cellular binding efficiency

The off-target payload delivery of γ-cyclodextrin metal organic framework (γ-CD-MOF) does not meet the requirements for targeted drug delivery applications. Herein, we synthesized γ-CD-MOF and crosslinked γ-CD-MOF (CL-γ-CD-MOF) to obtain the different sizes and different types of γ-CD-MOF. Furthermore, a simple post-modification method was applied to obtain the biofunctionalized γ-CD-MOFs to improve cellular interaction through hyaluronic acid (HA) for the first time. Various methods including measurement of different size of γ-CD-MOF, CL-γ-CD-MOF, and surface modified γ-CD-MOFs, followed by the characterization by various analytical techniques, drug absorption, cell viability, and cellular uptake studies, were performed to determine the functionality of the studied γ-CD-MOF-HA systems. The conjugation of γ-CD-MOF with HA (γ-CD-MOF-HA) showed a 4.8% higher average drug loading capacity than the γ-CD-MOF. It was found that the γ-CD-MOF-HA showed pH-responsive drug release and enhanced the cellular uptake of Doxorubicin (Dox) in HeLa cells. The present study results indicate the efficacy of the γ-CD-MOF-HA as a nano carrier, enabling a new direction for γ-CD-MOF to target the different tissues and cells.

Adaptation of the Kirkstall QV600 LLI Microfluidics System for the Study of Gastrointestinal Absorption by Mass Spectrometry Imaging and LC-MS/MS.

Absorption studies on oral drugs can be difficult due to the challenge of replicating the complex structure and environment of the GI tract. Drug absorption studies can be conducted using in vivo and ex vivo animal tissue or animal-free techniques. These studies typically involve the use of Caco-2 cells. However, Caco-2 cells do not incorporate all the cell types found in intestinal tissue and lack P450 metabolizing enzymes. The QV600 LLI system is a microfluidics system designed for use with cell culture. Here, it has been adapted to house appropriate sections of ex vivo porcine tissue to act as a system that models the duodenum section of the small intestine. A pH regulated solution of Atorvastatin was flowed over the apical layer of the GI tissue and a nutrient solution flowed over the basal layer of the tissue to maintain tissue viability. The tissue samples were snap-frozen, cryosectioned, and imaged using MALDI Mass Spectrometry Imaging (MSI). A proof-of-concept study on the effect of excipients on absorption was conducted. Different concentrations of the solubilizing agent were added to the donor circuit of the QV600 LLI. The amount of Atorvastatin in the acceptor circuit was determined to study the effect of the excipient on the amount of drug that had permeated through the tissue. Using these data, Papp, pig values were calculated and compared with the literature.

Coupling 1D blood circulation model and substance absorption model to study drug metabolization

The introduction of substances into the bloodstream initiates a complex series of chemical reactions. The study of drug absorption, metabolization and excretion processes is relevant for a better understanding of current treatments, by providing a better understanding, which helps improve them or propose new methods. In this project we propose a novel model for drug absorption, which is obtained by coupling a ID full-body blood flow model with the Wagner-Nelson absorption equation for a single compartment model through two established elimination rates Ket. For our experiments, we take the constant values from previous studies on the intravenous administration of ibuprofen and epinephrine, having Ket = 0.32 per hour, and Ket = 0.2 per minute respectively, and one large Ket = 3200 per hour to test absorption in a detailed full-body model. Our result plots show a decay in the concentration of drug over the time, which reflects the correct coupling of our models with the subtraction of drug amounts and the update of the current drug concentration by the absorption model over our ID blood flow model. To overcome resources limitations, we run our simulations for short periods of time, with an increased Ket value in the same order to generate an accelerated decay of the drug concentration in a more detailed model.

Best practices in current models mimicking drug permeability in the gastrointestinal tract - An UNGAP review

The absorption of orally administered drug products is a complex, dynamic process, dependant on a range of biopharmaceutical properties; notably the aqueous solubility of a molecule, stability within the gastrointestinal tract (GIT) and permeability. From a regulatory perspective, the concept of high intestinal permeability is intrinsically linked to the fraction of the oral dose absorbed. The relationship between permeability and the extent of absorption means that experimental models of permeability have regularly been used as a surrogate measure to estimate the fraction absorbed. Accurate assessment of a molecule's intestinal permeability is of critical importance during the pharmaceutical development process of oral drug products, and the current review provides a critique of in vivo, in vitro and ex vivo approaches. The usefulness of in silico models to predict drug permeability is also discussed and an overview of solvent systems used in permeability assessments is provided. Studies of drug absorption in humans are an indirect indicator of intestinal permeability, but both in vitro and ex vivo tools provide initial screening approaches and are important tools for assessment of permeability in drug development. Continued refinement of the accuracy of in silico approaches and their validation with human in vivo data will facilitate more efficient characterisation of permeability earlier in the drug development process and will provide useful inputs for integrated, end-to-end absorption modelling.

Integration of advanced methods and models to study drug absorption and related processes: An UNGAP perspective

This collection of contributions from the European Network on Understanding Gastrointestinal Absorption-related Processes (UNGAP) community assembly aims to provide information on some of the current and newer methods employed to study the behaviour of medicines. It is the product of interactions in the immediate pre-Covid period when UNGAP members were able to meet and set up workshops and to discuss progress across the disciplines. UNGAP activities are divided into work packages that cover special treatment populations, absorption processes in different regions of the gut, the development of advanced formulations and the integration of food and pharmaceutical scientists in the food-drug interface. This involves both new and established technical approaches in which we have attempted to define best practice and highlight areas where further research is needed. Over the last months we have been able to reflect on some of the key innovative approaches which we were tasked with mapping, including theoretical, in silico, in vitro, in vivo and ex vivo, preclinical and clinical approaches. This is the product of some of us in a snapshot of where UNGAP has travelled and what aspects of innovative technologies are important. It is not a comprehensive review of all methods used in research to study drug dissolution and absorption, but provides an ample panorama of current and advanced methods generally and potentially useful in this area. This collection starts from a consideration of advances in a priori approaches: an understanding of the molecular properties of the compound to predict biological characteristics relevant to absorption. The next four sections discuss a major activity in the UNGAP initiative, the pursuit of more representative conditions to study lumenal dissolution of drug formulations developed independently by academic teams. They are important because they illustrate examples of in vitro simulation systems that have begun to provide a useful understanding of formulation behaviour in the upper GI tract for industry. The Leuven team highlights the importance of the physiology of the digestive tract, as they describe the relevance of gastric and intestinal fluids on the behaviour of drugs along the tract. This provides the introduction to microdosing as an early tool to study drug disposition. Microdosing in oncology is starting to use gamma-emitting tracers, which provides a link through SPECT to the next section on nuclear medicine. The last two papers link the modelling approaches used by the pharmaceutical industry, in silico to Pop-PK linking to Darwich and Aarons, who provide discussion on pharmacometric modelling, completing the loop of molecule to man.

In-Silico Prediction of Oral Drug Bioavailability: A multi-boluses approach

This work focuses on a new mathematical model able to describe in a simple manner the intestinal physiology, in order to better study drug absorption and bioavailability. The aim of our model is to overcome the limitations of physiological pharmacokinetics models of the literature, introducing a different modelling approach. The core of the new proposed model is a Discrete-Continuous Approach (DCA): a sequence of boluses travels in the investigated portion of the intestine, in counter-current with blood that flows in continuous mode. No empirical equations are implemented in this model. Simulation results show an excellent correlation between the predicted and experimental concentration profile used to validate our model. Our new approach provides a simple tool, with a good reliability, to analyze a very complex phenomenon, using only few parameters.

Mucus-producing 3D cell culture models

In vitro cell-based models have been used for a long time since they are normally easily obtained and have an advantageous cost-benefit. Besides, they can serve a variety of ends, from studying drug absorption and metabolism to disease modeling. However, some in vitro models are too simplistic, not accurately representing the living tissues. It has been shown, mainly in the last years, that fully mimicking a tissue composition and architecture can be paramount for cellular behavior and, consequently, for the outcomes of the studies using such models. Because of this, 3D in vitro cell models have been gaining much attention, since they are able to better replicate the in vivo environment. In this review we focus on 3D models that contain mucus-producing cells, as mucus can play a pivotal role in drug absorption. Being frequently overlooked, this viscous fluid can have an impact on drug delivery. Thus, the aim of this review is to understand to which extent can mucus affect mucosal drug delivery and to provide a state-of-the-art report on the existing 3D cell-based mucus models.

Research work at the Center for Personalized Precision Medicine of Tuberculosis (cPMTb)

Tuberculosis (TB) is a leading cause of death worldwide and South Korea has the highest incidence and mortality rate of the disease of all the OECD countries. Professor Jae-Gook Shin is a pharmacologist based at the Center for Personalized Precision Medicine of Tuberculosis (cPMTb), which was established based on the premise of adopting a personalised approach to TB prevention and treatment. A key focus for Shin and his collaborators is personalised precision treatment and monitoring of TB patients, with 67 professors and clinicians from 20 clinical research cohort sites in the Republic of Korea involved in this pursuit. cPMTb has 30 years' personalised precision medicine R&D experience behind it. In their work, the researchers are using model-informed precision dosing to allow for the initial dose suggestion and then a dose adjustment during treatment for TB. Their personalised approach involves the use of epidemiological and clinical information, biochemical testing and genetic profiles of individuals. The goal is to improve the effectiveness of treatment and also reduce adverse drug reactions. A 'bench-to-bedside' approach is taken, with cPMTb's central laboratory facilitating in vitro and in vivo drug absorption, distribution, metabolism and excretion (ADME) studies as well as genotyping. This has meant that the researchers have been able to validate the role of NAT2 and SLCO1B1 variants in the cPMTb cohort. The team has been successful in establishing a hollow fibre infection model for TB research and will expand this work to support personalised dosing using clinical isolates.