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Drug delivery through electroporation could be highly beneficial for the treatment of different types of diseased tissues within the human body. In this work, a mathematical model of reversible tissue electroporation is presented for injecting drug into the diseased cells. The model emphasizes the tissue boundary where the drug is injected as a point source. In addition, the effect of drug loss at tissue boundaries through extracellular space is studied elaborately. Multiple pulses are applied to deliver a sufficient amount of drug into the targeted cells. The set of differential equations that model the physical circumstances are solved numerically. This model obtains a mass transfer coefficient (MTC), in terms of pore fraction coefficient and drug permeability that controls the drug transport from extracellular to intracellular space. The drug penetration throughout the tissue is captured for the application of different pulses. The boundary effects on drug concentration are highlighted in this study. The advocated model is able to perform homogeneous drug transport into the cells so that the affected tissue is treated completely. This model can be applied to optimize clinical experiments by avoiding the lengthy and costly in vivo and in vitro experiments. [ABSTRACT FROM AUTHOR]

Introduction: Therapeutic plasma exchange (TPE) eliminates disease‐contributing substances but may also affect drug concentrations. This study aimed to assess the prevalence of prescription drugs removable via TPE by reviewing patient medication histories. Methods: A retrospective, single‐center study was conducted from January 1, 2021 to December 31, 2022. The study included 244 patients undergoing 1087 TPE sessions. Drugs prescribed to patients on TPE days were categorized as "yes" (probably removable), "maybe" (possibly removable), and "no" (unlikely removable) regarding their removability via TPE. Results: Among 3966 prescriptions, 556 (14.0%) were analyzed, with 21.8%, 36.5%, and 41.7% falling into the "yes," "maybe," and "no" categories for removability. Although only 14.0% were categorized, 83.6% of patients received at least one analyzable drug. Among them, 83.8% had at least one potentially removable drug. Conclusion: Real‐world data highlights the need for caution in drug treatments during TPE to ensure optimal therapeutic outcomes, particularly for specific drugs. [ABSTRACT FROM AUTHOR]

[Display omitted] Developing new nanoplatforms for dynamically and quantitatively visualizing drug accumulation and targeting within tumors is crucial for precision cancer theranostic. However, achieving efficient tumor therapy via synergistic photothermal/photodynamic therapy (PTT/PDT) using a single excitation light source, remains a challenge. In this work, we designed Gd-surface functionalized copper sulfide nanoparticles that were modified with folic acid (FA) (Cu 1.96 S-Gd@FA) to overcome the above limitations and promote PTT/PDT therapeutics. Here, Cu 1.96 S-Gd nanoparticles were synthesized via a coprecipitation method. All samples exhibited high longitudinal relaxivity (up to 12.9 mM−1 s−1) and strong photothermal conversion efficiency (50.6%). Furthermore, the Gd ions promoted electron-hole segregation, inducing the Cu 1.96 S-Gd nanoparticles to generate more reactive oxygen species (ROS) than pure Cu 1.96 S nanoparticles. The Cu 1.96 S-Gd@FA enabled the targeting of folate receptor (FR) and promoted cellular uptake, consequently enhancing oncotherapy efficacy. Compared to non-targeted Cu 1.96 S-Gd, a higher signal enhancement for magnetic resonance (MR) imaging in vivo by Cu 1.96 S-Gd@FA was recorded. Given photothermal ability, the nanoparticles also could be visualized in infrared (IR) imaging. Furthermore, the nanoparticles exhibited biodegradation behavior and achieved good drug elimination performance via renal clearance. Our strategy, integrating Cu 1.96 S-Gd@FA nanoparticles, MR/IR dual-modal imaging, and PTT/PDT into one nanoplatform, demonstrated great potential for anti-breast cancer therapy by effectively targeting FR overexpressed breast cancer cells. [ABSTRACT FROM AUTHOR]

The Biopharmaceutics Drug Disposition Classification System (BDDCS) can be utilized to predict drug disposition, including interactions with other drugs and transporter or metabolizing enzyme effects based on the extent of metabolism and solubility of a drug. However, defining the extent of metabolism relies upon clinical data. Drugs exhibiting high passive intestinal permeability rates are extensively metabolized. Therefore, we aimed to determine if in vitro measures of permeability rate or in silico permeability rate predictions could predict the extent of metabolism, to determine a reference compound representing the permeability rate above which compounds would be expected to be extensively metabolized, and to predict the major route of elimination of compounds in a two-tier approach utilizing permeability rate and a previously published model predicting the major route of elimination of parent drug. Twenty-two in vitro permeability rate measurement data sets in Caco-2 and MDCK cell lines and PAMPA were collected from the literature, while in silico permeability rate predictions were calculated using ADMET Predictor or VolSurf+. The potential for permeability rate to differentiate between extensively and poorly metabolized compounds was analyzed with receiver operating characteristic curves. Compounds that yielded the highest sensitivity-specificity average were selected as permeability rate reference standards. The major route of elimination of poorly permeable drugs was predicted by our previously published model, and the accuracies and predictive values were calculated. The areas under the receiver operating curves were >0.90 for in vitro measures of permeability rate and >0.80 for the VolSurf+ model of permeability rate, indicating they were able to predict the extent of metabolism of compounds. Labetalol and zidovudine predicted greater than 80% of extensively metabolized drugs correctly and greater than 80% of poorly metabolized drugs correctly in Caco-2 and MDCK, respectively, while theophylline predicted greater than 80% of extensively and poorly metabolized drugs correctly in PAMPA. A two-tier approach predicting elimination route predicts 72 ± 9%, 49 ± 10%, and 66 ± 7% of extensively metabolized, biliarily eliminated, and renally eliminated parent drugs correctly when the permeability rate is predicted in silico and 74 ± 7%, 85 ± 2%, and 73 ± 8% of extensively metabolized, biliarily eliminated, and renally eliminated parent drugs correctly when the permeability rate is determined in vitro.

Extracorporeal blood purification is considered an adjunct therapy in critically ill patients with life-threatening conditions such as sepsis and septic shock. It consists of cytokine removal, removal of endotoxins, a combination of both, or the removal of pathogens themselves. The latter technique was introduced for clinical application very recently. This case study describes a case of a 69-year-old female lung transplant recipient patient with a persistent VV-ECMO-related septic deep vein thrombosis with continuous renal replacement therapy-dependent acute kidney injury initiated on the Seraph®-100 Microbind Affinity Filter in order to control the persistent bacteraemia with coagulase-negative staphylococci. Drug plasma concentrations (vancomycin, tacrolimus, and mycophenolic acid) were measured before and after the device to calculate absorber-related drug clearance. [ABSTRACT FROM AUTHOR]

Key summary points: Aim: To summarize the main age-associated changes in drug metabolism and elimination and discuss their possible incorporation into personalised prescribing tools for the older patient population. Findings: There is currently limited knowledge regarding the impact of frailty, pharmacogenomics, drug–drug, drug–disease, and organ–organ interactions, on drug metabolism and elimination in the older population, particularly in subjects >80 years. However, easily measurable age-associated pharmacokinetic changes, particularly the reduced clearance of renally eliminated drugs, could be soon incorporated into personalised prescribing tools. Message: Despite ongoing progress in the field, additional studies are required to justify the routine incorporation of data pertaining to drug metabolism and elimination into personalised prescribing tools for older patients. Purpose: We discuss the known age-associated changes in drug metabolism and elimination, the potential use of this information when selecting specific therapeutic strategies in older patients, and the steps required to fill the knowledge gap in this field. Methods: We conducted a narrative review that encapsulates the current knowledge regarding the main age-associated changes in drug metabolism and elimination and discusses their possible inclusion in current and future personalised prescribing tools for the older patient population. Results: Despite some progress in this field, the lack of specific information regarding the impact of frailty, pharmacogenomics, and drug–drug, drug–disease, and organ–organ interactions, particularly in subjects > 80 years, currently prevents the routine incorporation of pharmacokinetic data, barring measures of renal function, into personalised prescribing tools. Conclusions: The incorporation of pharmacokinetic data into personalised prescribing, an approach based on the consideration of a number of patient's characteristics when selecting the right drug(s) and dose regimen(s) to maximize effectiveness and limit toxicity, remains a hypothetical construct in geriatric care. Pending the inclusion of frail and complex older patients in pre- and post-marketing studies, a better understanding of the key pharmacokinetic alterations of common medications in "real-life" patients, together with the implementation of effective strategies tackling inappropriate prescribing, is likely to improve clinical outcomes and reduce healthcare utilization in the older population. [ABSTRACT FROM AUTHOR]

Activated charcoal both reduces primary drug absorption and enhances drug elimination. However, the two mechanisms of action overlap and are indistinguishable from each other. In order to estimate the extend of enhanced elimination, we summarized the effect of activated charcoal on intravenously administered drugs, where reduced drug exposure can be attributed to enhanced elimination. We performed a meta‐analysis of randomized controlled studies evaluating the effect of orally administered activated charcoal on the systemic exposure of intravenously administered drugs. We searched the bibliographic databases PubMed, Embase and Cochrane. Meta‐regression analyses of selected physiochemical drug properties on the effect sizes of activated charcoal were performed. All but one of 21 included studies used multiple‐dose activated charcoal (MDAC). MDAC reduced the median half‐life of the intravenously administered study drugs by 45.7% (interquartile range: 15.3%‐51.3%) and area under the concentration time curve by 47.0% (interquartile range: 36.4%‐50.2%). MDAC significantly improved drug elimination across nine different intravenously administered drugs, but we were unable to identify factors allowing extrapolation to other drugs. The results offer a possible and plausible rationale for the previously observed effects of single‐dose activated charcoal beyond the timeframe where ingested drug is present in the gastro‐intestinal tract. [ABSTRACT FROM AUTHOR]

Abstract Background Fish are vulnerable to stress from over-crowding during transportation and eugenol is the most common sedative used to minimize fish injury. The ADI value of 2.5 mg/kg is recommended by the Joint FAO/WHO Expert Committee on Food Additives. The aim of this work was to study the elimination kinetics of eugenol following exposure of grass carp to a eugenol bath in a simulated transportation setting. Results Grass carp, Ctenopharyngodon idella (120 fish) were exposed for 24 h to a 10 mg/L eugenol bath. Sampling was performed during a 96 h period after the 24 h bath. Eight fish were sampled at each time point and muscle, plasma and liver concentrations of the drug were determined by ultra-performance liquid chromatography-tandem mass spectrometry. The concentration-time data of eugenol in each tissue were analyzed using non-compartmental methods. The peak concentrations (Cmax) in plasma, muscle and liver were 7.68, 5.30 and 24.63 mg/kg and the elimination half-lives (t1/2β) were 19.79, 10.27 and 55.28 h, respectively. The clearance (CL) values were 0.10, 0.44 and 0.04 L/h/kg and the areas under the concentration-time curve (AUC0-96h) were 91.54, 22.44, and 214.12 mg·h/L in plasma, muscle and liver, respectively. After a eugenol exposure bath, drug concentrations in muscle tissue of grass carp were below 1 mg/kg at 8 h and 0.1 mg/kg at 24 h. Conclusions The drug concentrations in muscle tissue at 8 h were lower than the recommended ADI value.

Background: Paclitaxel (PTX) products currently approved by the Food and Drug Administration include Kolliphor EL-paclitaxel micelles (KoEL-paclitaxel, Taxol) and nanoparticle albumin-bound paclitaxel (nab-paclitaxel, Abraxane). Despite containing the same cytotoxic agent, different PTX formulations have distinct pharmacological responses and indications in patients with cancer. Several novel PTX delivery vehicles that have shown superior efficacy to Taxol in animal models failed to demonstrate efficacy in Phase II/III human clinical trials. Materials and methods: A 10 mg/kg IV dose of KoEL-paclitaxel or nab-paclitaxel was administered to mice, and the pharmacokinetics (PK) profile of PTX in mice was then compared with the human PK profile from clinical studies. Population PK model and simulation was used to delineate the distribution and elimination characteristics in each species. In addition, tumor shrinkage was measured after weekly administration of both formulations in mouse xenograft model. Results: Our pharmacokinetic modeling results suggested that elimination predominates over distribution in driving PTX disposition in mice, hence restricting the PTX tissue accumulation. Moreover, the rapid elimination of PTX in mice minimized the different formulation effects on PTX tissue distribution, which is believed to link to the superior efficacy of nab-paclitaxel over KoEL-paclitaxel seen in human. In contrast to mice, PTX distribution predominates over elimination in human, and the decline in plasma PTX concentration reflected the deeper tissue distribution by nab-paclitaxel.Conclusion: This species difference in PTX distribution and elimination hinders a simple direct extrapolation from animals to humans. Therefore, species difference in drug distribution and elimination should be carefully assessed during translational drug development. [ABSTRACT FROM AUTHOR]

As an effective treatment for acute gouty arthritis and cardiovascular disease, colchicine is also a toxic alkaloid and may cause poisoning or even death in overdose. The study of colchicine elimination and the diagnosis of poisoning etiology need the rapid and accurate quantitative analysis method in biological matrix. An analytical method was developed for colchicine in plasma and urine by in-syringe dispersive solid phase extraction (DSPE) followed by liquid chromatography-triple quadrupole mass spectrometry (LC-MS/MS). Sample extraction and protein precipitation were proceeded with acetonitrile. The extract was cleaned by in-syringe DSPE. An XBridge™ BEH C 18 column（100 mm × 2.1 mm, 2.5 µm）was used to separate colchicine by gradient elution with mobile phase of 0.01% (v/v) ammonia-methanol. The amount and filling sequence of magnesium sulfate (MgSO 4) and primary secondary amine (PSA) suitable for in-syringe DSPE were studied. Scopolamine was screened as the quantitative internal standard (IS) for colchicine analysis according to the consistency of recovery rate, chromatographic retention time and matrix effects. The limits of detection for colchicine in plasma and urine were both 0.06 ng mL−1 and the limits of quantitation were both 0.2 ng mL−1. The linear range was 0.04 – 20 ng mL−1 (Equivalent to 0.2–100 ng mL−1 in plasma or urine) with a correlation coefficient r > 0.999. By IS calibration, the average recoveries at three spiking levels in plasma and urine were 95.3–102.68% and 93.9–94.8% with the relative standard deviations (RSDs) of 2.9–5.7% and 2.3–3.4%, respectively. The matrix effects, stability, dilution effects and carryover for determination of colchicine in plasma and urine were also evaluated. The elimination of colchicine within 72–384 h post-ingestion was studied for a poisoning patient with the doses of 1 mg d−1 for 39 days and then 3 mg d−1 for 15 days). • Colchicine was determined in plasma and urine by LC-MS/MS. • Samples are pretreated with in-syringe dispersive solid phase extraction cleanup. • Scopolamine was screened as the internal standard. • Colchicine elimination from plasma and urine of a poisoning patient was studied. [ABSTRACT FROM AUTHOR]

Solute dispersion is a significant phenomenon during drug targeting to estimate the accumulation of drug particles at the tumour region with the capture efficiency. In this present study, we aim to predict the effective dispersion and saturated concentration of drug carriers during magnetic drug targeting in a microvessel with a time fractional derivative based dispersion model. The magnetic nanoparticles are bound with the non-magnetic materials/microgels with the therapeutic agents to prepare the drug carriers. A magnetic field is created outside the body to control and accelerate the trajectories of the drug carriers. The nature of the blood flow into the vessel is considered as Casson fluid. The velocity of the drug carriers is solved analytically, while the fractional-order dispersion equation is computed numerically using the finite difference technique with the forward time and central space discretization. The influence of fractional-order parameter and model biological parameters such as rheological parameter, permeability parameter related to hydraulic conductivity, magnetization, volume fraction of nanoparticles, tumour-magnet distance, nanoparticle radius, drug elimination, and source term on the relative effective dispersion are discussed. The outcomes showed that both rheological parameters and volume fraction increase drug carrier particle concentration, and that saturating occurs at a later time as they increase. Higher magnetization, permeability parameter related to the hydraulic conductivity, and source term are associated with faster transportation of drug carriers to the tumour site. In addition, we note that by using small particle sizes, a high concentration of the drug-coated nanoparticles will be expected in the tumour area, and this slows the rate at which it reaches the saturation point. [Display omitted] • A fractionalized dispersion equation describes drug delivery in a tumour region. • Non-Newtonian Casson model is used to describe the rheology of the blood. • A Darcy model used to define the permeability of the microvessel. • A memory effect is associated with increase in concentration of drug carriers. • Drug delivery in the tumour region is greatly influenced by biological parameters. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate organic anion transporter-mediated drug-drug interaction (DDI) potential for individual active components of Danshen ( Salvia miltiorrhiza) vs. combinations using in vitro and in silico approaches. Methods: Inhibition profiles for single Danshen components and combinations were generated in stably-expressing human (h)OAT1 and hOAT3 cells. Plasma concentration-time profiles for compounds were estimated from in vivo human data using an i.v. two-compartment model (with first-order elimination). The cumulative DDI index was proposed as an indicator of DDI potential for combination products. This index was used to evaluate the DDI potential for Danshen injectables from 16 different manufacturers and 14 different lots from a single manufacturer. Results: The cumulative DDI index predicted in vivo inhibition potentials, 82% (hOAT1) and 74% (hOAT3), comparable with those observed in vitro, 72 ± 7% (hOAT1) and 81 ± 10% (hOAT3), for Danshen component combinations. Using simulated unbound C values, a wide range in cumulative DDI index between manufacturers, and between lots, was predicted. Many products exhibited a cumulative DDI index > 1 (50% inhibition). Conclusions: Danshen injectables will likely exhibit strong potential to inhibit hOAT1 and hOAT3 function in vivo. The proposed cumulative DDI index might improve prediction of DDI potential of herbal medicines or pharmaceutical preparations containing multiple components. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To investigate whether YouTube videos on pharmacokinetics can be a useful learning resource for medical students. METHODS: YouTube was searched from 01 November to 15 November 2013 for search terms "Pharmacokinetics", "Drug absorption", "Drug distribution", Drug metabolism", "Drug elimination", "Biliary excretion of drugs", and Renal excretion of drugs". Only videos in the English and those matching the inclusion criteria were included. For each video, the following characteristic data were collected: title, URL, duration, number of viewers, date uploaded, and viewership per day, like, dislike, number of comments, number of video sharing, and the uploader /creator. Using standardized criteria comprising technical, content, authority and pedagogy parameters, three evaluators independently assessed the videos for educational usefulness. Data were analyzed using SPSS software and the agreement between the evaluators was calculated using Cohen's kappa analysis. RESULTS: The search identified 1460 videos. Of these, only 48 fulfilled the inclusion criteria. Only 30 were classified as educationally useful videos (62.5%) scoring 13.83±0.45 (mean±SD) while the remaining 18 videos were not educationally useful (37.5%) scoring 6.48±1.64 (mean±SD), p = 0.000. The educationally useful videos were created by pharmacologists/educators 83.3% (25/30), professors from two universities 13.3% (04/30) and private tutoring body 3.3% (01/30). The useful videos were viewed by 12096 (65.4%) and had a total of 433332 days on YouTube, while the non-educationally useful videos were viewed by 6378 (34.6%) viewers and had 20684 days on YouTube. No correlation was found between video total score and number of like (R² 0.258), dislike (R² 0.103), viewers (R² 0.186), viewership/day (R² 0.256), comments (R² 0.250), or share (R² 0.174). The agreement between the three evaluators had an overall Cohen's kappa score in the range of 0.582-0.949. CONCLUSIONS: YouTube videos on pharmacokinetics and drug elimination showed a range of variability in regard to the contents of their educational usefulness. Medical educators should be aware of the potential influence of YouTube videos may have on student's understanding of pharmacokinetics and drug elimination. Users who rely on the comments made by viewers or the approval expressed in terms of the number of like given by viewers should become aware that these indicators are not accurate and do not correlate with the scores given to videos. [ABSTRACT FROM AUTHOR]

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Abstract There is a growing movement within biology to transform the undergraduate curriculum. A major goal is to actively engage students so that they perceive biology as an evidence-based science with testable hypotheses that are supported by experimental data. This resource is the fourth module in a series that engages students in inquiry-based activities to introduce them to the process of scientific modeling and validation. The modules are a self-contained series of self-study guides for undergraduates, both with and without calculus. The modules are designed so that students can complete them without additional assistance, making them suitable for use as stand-alone biophysics computer labs or for a discovery-based active-learning course. In this module, students learn the basics of the one-compartment model of pharmacokinetics and why it predicts an exponential decay. Students compare the models predictions with experimental data for the elimination of piperacillin in healthy volunteers. During the data analysis, students discover that the fitted initial concentration predicts the distribution volume, that the fitted rate constant predicts the drug half-life, and the utility of semi-log plots. Students use graphical residual analysis to discover systematic deviations in the original fit. By reanalyzing the longer-time serum-only data, students discover that the systematic errors in the fit can be eliminated, indicating the true range of applicability of the model. This module is the fourth in a series that are being developed with the support of a National Science Foundation Course, Curriculum, and Laboratory Improvement grant. The modules are based on teaching materials I've been working on over the last 8 years for my undergraduate biophysics classes. These new courses have been developed in response to a movement within the biological sciences that calls for more quantitative content for undergraduates in biological and health sciences. I have found this module to be extremely effective in the three semesters that I have used it in my undergraduate classroom. Student engagement with the material is high as they can readily appreciate the significance of the data analyzed in the module. Students also respond well to the active-learning approach. By actually doing the fits themselves, they gain a more detailed understanding of the scientific process of model development and validation. Many have reported gaining real satisfaction in discovering new insights about the experimental results (that were not quantitatively compared with any pharmacokinetic model).

Study of time course of a drug and its metabolites in the body after administration by any route is referred to as pharmacokinetics. Since response to any drug is a function of concentration of that drug in biophase, the aim of pharmacokinetics has been to determine what dose and dosing schedule are sufficient to elicit and maintain a desired clinical response. Pharmacokinetics mainly involves applications of calculus to derive different parameters and equations. Most of the pharmacy, medical, veterinary, and/or dental students, being unacquainted with calculus, fail to comprehend the basic concepts of pharmacokinetics. Therefore, an attempt has been made to derive some basic information regarding drug decline and drug accumulation with the help of algebraic concepts using geometric series for deriving and explaining the kinetic parameters. The article has been supported with some numerical examples for better understanding of the concept. [ABSTRACT FROM AUTHOR]