Displaying publications 341 - 360 of 525 in total

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  1. The effect of physical stability and modified gastrointestinal tract behaviour of resveratrol-loaded NLCs encapsulated alginate beads
    Manikandan S, Jose PA, Karuppaiah A, Rahman H
    Naunyn Schmiedebergs Arch Pharmacol, 2024 Nov;397(11):9007-9021.
    PMID: 38878088 DOI: 10.1007/s00210-024-03223-3
    Nanostructured lipid carriers (NLC) have low storage and gastrointestinal stability, limiting their applicability. The work aimed to elevate the stability and behaviour of NLC in the alimentary tract by creating an alginate bead. Through the extrusion dropping procedure, Resveratrol (RES)-loaded NLC were efficiently integrated into alginate beads. The incorporation had no significant impact on the particle size, morphology, or inner structure of NLC, as assessed using DLS (Dynamic Light Scattering), SEM (Scanning Electron Microscopy), Differential Scanning Calorimetry (DSC) and FT-IR (Fourier Transform Infra-Red). Incorporating NLC into alginate beads improves its physical stability compared to dispersion of NLC as well as NLC-Sol. An in vitro release investigation found that the NLC-alginate beads released RES more slowly than optimized NLC formulation (RES-NLCs-opt) and NLC-alginate sol. Research on simulated in vitro digestive models revealed that just a small amount of integrated NLC may permeate stomach fluid due to its tiny size. The slow diffusion of NLC from alginate to intestinal fluid prevented aggregation and allowed for gentle hydrolysis of the lipid matrix. Incorporating NLC in alginate beads shows promise for improving stability, modifying gastrointestinal behaviour, and controlling release throughout the process of digestion.
    Matched MeSH terms: Stilbenes/pharmacokinetics
  2. An Ocular Exposure Prediction for Topical Atropine in Human Using Physiologically Based Pharmacokinetic Modeling
    Zheng A, Han T, Bu F, He Q, Shang J, Ho PCL, et al.
    AAPS J, 2025 May 02;27(4):89.
    PMID: 40316760 DOI: 10.1208/s12248-025-01052-7
    Developing a mathematical model to predict the distribution and bioavailability of atropine in human eyes is an insight approach for clinical practice. This study aims to develop a human ocular physiologically based pharmacokinetic (PBPK) modeling for the ophthalmic drug atropine and explore possible mechanisms by which atropine reduces myopia progression in children. The Ocular Compartment Absorption and Transit (OCAT™) model was employed to describe the ocular distribution of atropine following administration at different dosages in both rabbits and humans. The PBPK model enables the extrapolation of pharmacokinetic characteristics among different species depending on theirphysiology and anatomy. The developed and validated OCAT-PBPK model demonstrated good agreement with observed data from rabbit ocular tissues and human aqueous humor. Fifty-eight percent of simulations fell within the standard deviation range of experimental data. The extrapolated human PBPK model for accurately predicted the ocular exposure and distribution following the administration of low-concentration atropine. This study confirms the performance of the ocular PBPK model in predicting ocular pharmacokinetic behavior among different species. Model's predictions indicate that atropine shows significant potential to penetrate the posterior eye segment, providing underlying insights into its mechanisms of action in the eye.
    Matched MeSH terms: Ophthalmic Solutions/pharmacokinetics
  3. Lycopene loaded whey protein isolate nanoparticles: An innovative endeavor for enhanced bioavailability of lycopene and anti-cancer activity
    Jain A, Sharma G, Ghoshal G, Kesharwani P, Singh B, Shivhare US, et al.
    Int J Pharm, 2018 Jul 30;546(1-2):97-105.
    PMID: 29715533 DOI: 10.1016/j.ijpharm.2018.04.061
    The work entails a novel strategy of formulating the lycopene loaded whey protein isolate nanoparticles (LYC-WPI-NPs) solely using the rational blend of biomacromolecule without using equipment-intensive techniques. The LYC-WPI-NPs were fabricated as a substantial drug delivery platform, with maximum entrapment, spatial and controlled release manners, exceptional plasma concentration, and perspective for discrepancy delivery of therapeutics. Prepared nano-formulations were measured in ultra-fine size (100-350 nm) with sphere-shaped. The percent lycopene entrapment of prepared LYC-WPI-NPs was estimated in the range to 50 and 65%. In vitro percent cumulative release study demonstrated deaden and extended release i.e. approximately 75% following 16th h. The in vitro percent cell survival (cytotoxicity study) of prepared nanoparticles was evaluated against MCF-7 breast cancer cells by MTT based colorimetric assay. Sub-cellular localization of lycopene when delivered by LYC-WPI-NPs was assessed by HPLC (high performance liquid chromatography). The WPI-NPs enhance the oral bioavailability of lycopene by controlling its release from nano-formulation and facilitating its absorption through lymphatic pathways. Prophylactic anticancer efficacy of LYC-WPI-NPs was evaluated thereafter on experimentally induced breast cancer animal model. Conclusively, it may quite reasonable that lycopene loaded protein nanoparticles are competent to improve the biopharmaceutical attributes of lycopene and demonstrated prophylactic anticancer activity, decrease tumor proliferation and increase the survival rate of treated animals, thus signifying their feasible usefulness in cancer therapeutic and intervention.
    Matched MeSH terms: Whey Proteins/pharmacokinetics; Antineoplastic Agents/pharmacokinetics; Carotenoids/pharmacokinetics; Drug Carriers/pharmacokinetics
  4. Designing of promising medicinal scaffolds for Alzheimer's disease through enzyme inhibition, lead optimization, molecular docking and dynamic simulation approaches
    Hassan M, Abbasi MA, Aziz-Ur-Rehman, Siddiqui SZ, Shahzadi S, Raza H, et al.
    Bioorg Chem, 2019 10;91:103138.
    PMID: 31446329 DOI: 10.1016/j.bioorg.2019.103138
    In the designed research work, a series of 2-furoyl piperazine based sulfonamide derivatives were synthesized as therapeutic agents to target the Alzheimer's disease. The structures of the newly synthesized compounds were characterized through spectral analysis and their inhibitory potential was evaluated against butyrylcholinesterase (BChE). The cytotoxicity of these sulfonamides was also ascertained through hemolysis of bovine red blood cells. Furthermore, compounds were inspected by Lipinki Rule and their binding profiles against BChE were discerned by molecular docking. The protein fluctuations in docking complexes were recognized by dynamic simulation. From our in vitro and in silico results 5c, 5j and 5k were identified as promising lead compounds for the treatment of targeted disease.
    Matched MeSH terms: Cholinesterase Inhibitors/pharmacokinetics; Piperazines/pharmacokinetics; Sulfonamides/pharmacokinetics; Nootropic Agents/pharmacokinetics
  5. Fulltext Pretreatment of Blumea lacera leaves ameliorate acute ulcer and oxidative stress in ethanol-induced Long-Evan rat: A combined experimental and chemico-biological interaction
    Hossen MA, Reza ASMA, Ahmed AMA, Islam MK, Jahan I, Hossain R, et al.
    Biomed Pharmacother, 2021 Mar;135:111211.
    PMID: 33421733 DOI: 10.1016/j.biopha.2020.111211
    Blumea lacera (Burm.f.) DC. is described as a valuable medicinal plant in various popular systems of medicine. The aim of the experiment reports the in vivo antiulcer activity of methanol extract of Blumea lacera (MEBLL) and in silico studies of bioactive constituents of MEBLL. In this study, fasted Long-Evans rat treated with 80 % ethanol (0.5 mL) to induce gastric ulcer, were pretreated orally with MEBLL at different doses (250 and 500 mg/kg, p.o., b.w) and omeprazole (20 mg/kg, p.o.) and distilled water were used as a reference drug and normal control respectively. In silico activity against gastric H+-K+ATPase enzyme was also studied. The findings demonstrated that the treatment with MEBLL attenuated markedly ulcer and protected the integrity of the gastric mucosa by preventing the mucosal ulceration altered biochemical parameters of gastric juice such total carbohydrate, total protein and pepsin activity. Additionally, the experimental groups significantly (p 
    Matched MeSH terms: Anti-Ulcer Agents/pharmacokinetics; Antioxidants/pharmacokinetics; Plant Extracts/pharmacokinetics; Proton Pump Inhibitors/pharmacokinetics
  6. Influence of lipolysis and droplet size on tocotrienol absorption from self-emulsifying formulations
    Yap SP, Yuen KH
    Int J Pharm, 2004 Aug 20;281(1-2):67-78.
    PMID: 15288344
    A single dose comparative bioavailability study was conducted to evaluate the bioavailability of tocotrienols from two self-emulsifying formulations, one of which produced an emulsion that readily lipolysed under in vitro condition (SES-A), while the other produced a finer dispersion with negligible lipolysis (SES-B) in comparison with that of a non-self-emulsifying formulation in soya oil. The study was conducted according to a three-way crossover design using six healthy human volunteers. Statistically significant differences were observed between the logarithmic transformed peak plasma concentration (Cmax) and total area under the plasma concentration-time curve (AUC(0-infinity)) values of both SES-A and -B compared to NSES-C indicating that SES-A and -B achieved a higher extent of absorption compared to NSES-C. Moreover, the 90% confidence interval of the AUC(0-infinity) values of both SES-A and -B over those of NSES-C were between 2-3 suggesting an increase in bioavailability of about two-three times compared to NSES-C. Both SES-A and -B also achieved a faster onset of absorption. However, both SES-A and -B had comparable bioavailability, despite the fact that SES-B was able to form emulsions with smaller droplet size. Thus, it appeared that both droplet sizes as well as the rate and extent of lipolysis of the emulsion products formed were important for enhancing the bioavailability of the tocotrienols from the self-emulsifying systems.
    Matched MeSH terms: Emulsions/pharmacokinetics; Polysorbates/pharmacokinetics; Soybean Oil/pharmacokinetics; Tocotrienols/pharmacokinetics*
  7. Stomach specific polymeric low density microballoons as a vector for extended delivery of rabeprazole and amoxicillin for treatment of peptic ulcer
    Choudhary S, Jain A, Amin MCIM, Mishra V, Agrawal GP, Kesharwani P
    Colloids Surf B Biointerfaces, 2016 May 01;141:268-277.
    PMID: 26859118 DOI: 10.1016/j.colsurfb.2016.01.048
    The study was intended to develop a new intra-gastric floating in situ microballoons system for controlled delivery of rabeprazole sodium and amoxicillin trihydrate for the treatment of peptic ulcer disease. Eudragit S-100 and hydroxypropyl methyl cellulose based low density microballoons systems were fabricated by employing varying concentrations of Eudragit S-100 and hydroxypropyl methyl cellulose, to which varying concentrations of drug was added, and formulated by stirring at various speed and time to optimize the process and formulation variable. The formulation variables like concentration and ratio of polymers significantly affected the in vitro drug release from the prepared floating device. The validation of the gastro-retentive potential of the prepared microballoons was carried out in rabbits by orally administration of microballoons formulation containing radio opaque material. The developed formulations showed improved buoyancy and lower ulcer index as compared to that seen with plain drugs. Ulcer protective efficacies were confirmed in ulcer-bearing mouse model. In conclusion, greater compatibility, higher gastro-retention and higher anti-ulcer activity of the presently fabricated formulations to improve potential of formulation for redefining ulcer treatment are presented here. These learning exposed a targeted and sustained drug delivery potential of prepared microballoons in gastric region for ulcer therapeutic intervention as corroborated by in vitro and in vivo findings and, thus, deserves further attention for improved ulcer treatment.
    Matched MeSH terms: Amoxicillin/pharmacokinetics*; Anti-Ulcer Agents/pharmacokinetics; Anti-Bacterial Agents/pharmacokinetics; Rabeprazole/pharmacokinetics*
  8. Fulltext Discovery of indolylpiperazinylpyrimidines with dual-target profiles at adenosine A2A and dopamine D2 receptors for Parkinson's disease treatment
    Shao YM, Ma X, Paira P, Tan A, Herr DR, Lim KL, et al.
    PLoS One, 2018;13(1):e0188212.
    PMID: 29304113 DOI: 10.1371/journal.pone.0188212
    Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra of the human brain, leading to depletion of dopamine production. Dopamine replacement therapy remains the mainstay for attenuation of PD symptoms. Nonetheless, the potential benefit of current pharmacotherapies is mostly limited by adverse side effects, such as drug-induced dyskinesia, motor fluctuations and psychosis. Non-dopaminergic receptors, such as human A2A adenosine receptors, have emerged as important therapeutic targets in potentiating therapeutic effects and reducing the unwanted side effects. In this study, new chemical entities targeting both human A2A adenosine receptor and dopamine D2 receptor were designed and evaluated. Two computational methods, namely support vector machine (SVM) models and Tanimoto similarity-based clustering analysis, were integrated for the identification of compounds containing indole-piperazine-pyrimidine (IPP) scaffold. Subsequent synthesis and testing resulted in compounds 5 and 6, which acted as human A2A adenosine receptor binders in the radioligand competition assay (Ki = 8.7-11.2 μM) as well as human dopamine D2 receptor binders in the artificial cell membrane assay (EC50 = 22.5-40.2 μM). Moreover, compound 5 showed improvement in movement and mitigation of the loss of dopaminergic neurons in Drosophila models of PD. Furthermore, in vitro toxicity studies on compounds 5 and 6 did not reveal any mutagenicity (up to 100 μM), hepatotoxicity (up to 30 μM) or cardiotoxicity (up to 30 μM).
    Matched MeSH terms: Adenylyl Cyclase Inhibitors/pharmacokinetics; Antiparkinson Agents/pharmacokinetics; Piperazines/pharmacokinetics; Pyrimidines/pharmacokinetics; Dopamine Agonists/pharmacokinetics; Adenosine A2 Receptor Antagonists/pharmacokinetics
  9. The contribution of adrenoceptor subtype(s) in the renal vasculature of diabetic spontaneously hypertensive rats
    Armenia A, Munavvar AS, Abdullah NA, Helmi A, Johns EJ
    Br J Pharmacol, 2004 Jun;142(4):719-26.
    PMID: 15172958
    1. Diabetes and hypertension are both associated with an increased risk of renal disease and are associated with neuropathies, which can cause defective autonomic control of major organs including the kidney. This study aimed to examine the alpha(1)-adrenoceptor subtype(s) involved in mediating adrenergically induced renal vasoconstriction in a rat model of diabetes and hypertension. 2. Male spontaneously hypertensive rats (SHR), 220-280 g, were anaesthetized with sodium pentobarbitone 7-day poststreptozotocin (55 mg x kg(-1) i.p.) treatment. The reductions in renal blood flow (RBF) induced by increasing frequencies of electrical renal nerve stimulation (RNS), close intrarenal bolus doses of noradrenaline (NA), phenylephrine (PE) or methoxamine were determined before and after administration of nitrendipine (Nit), 5-methylurapidil (5-MeU), chloroethylclonidine (CEC) and BMY 7378. 3. In the nondiabetic SHR group, mean arterial pressure (MAP) was 146+/-6 mmHg, RBF was 28.0+/-1.4 ml x min(-1) x kg(-1) and blood glucose was 112.3+/-4.7 mg x dl(-1), and in the diabetic SHR Group, MAP was 144+/-3 mmHg, RBF 26.9+/-1.3 ml(-1) min x kg(-1) and blood glucose 316.2+/-10.5 mg x dl(-1). Nit, 5-MeU and BMY 7378 blunted all the adrenergically induced renal vasoconstrictor responses in SHR and diabetic SHR by 25-35% (all P<0.05), but in diabetic rats the responses induced by RNS and NA treated with 5-MeU were not changed. By contrast, during the administration of CEC, vasoconstrictor responses to all agonists were enhanced by 20-25% (all P<0.05) in both the SHR and diabetic SHR. 4. These findings suggest that alpha(1A) and alpha(1D)-adrenoceptor subtypes contribute in mediating the adrenergically induced constriction of the renal vasculature in both the SHR and diabetic SHR. There was also an indication of a greater contribution of presynaptic adrenoceptors, that is, alpha(1B)-, and/or alpha(2)-subtypes.
    Matched MeSH terms: Clonidine/pharmacokinetics; Methoxamine/pharmacokinetics; Nitrendipine/pharmacokinetics; Norepinephrine/pharmacokinetics; Phenylephrine/pharmacokinetics; Piperazines/pharmacokinetics
  10. Evaluation of in vitro efficacy of docetaxel-loaded calcium carbonate aragonite nanoparticles (DTX-CaCO3NP) on 4T1 mouse breast cancer cell line
    Hammadi NI, Abba Y, Hezmee MNM, Razak ISA, Kura AU, Zakaria ZAB
    In Vitro Cell Dev Biol Anim, 2017 Dec;53(10):896-907.
    PMID: 28916966 DOI: 10.1007/s11626-017-0197-3
    Cockle shell-derived calcium carbonate nanoparticles have shown promising potentials as slow drug-releasing compounds in cancer chemotherapy. In this study, we evaluated the in vitro efficacy of docetaxel (DTX)-loaded CaCO3NP on 4T1 cell line. This was achieved by evaluating the following: cytotoxicity using MTT assay, fluorescence imaging, apoptosis with Annexin V assay, cell cycle analysis, scanning (SEM) and transmission electron microscopy (TEM), and scratch assay. Based on the results, DTX-CaCO3NP with a DTX concentration of 0.5 μg/mL and above had comparable cytotoxic effects with free DTX at 24 h, while all concentrations had similar cytotoxic effect on 4T1 cells at 48 and 72 h. Fluorescence and apoptosis assay showed a higher (p 
    Matched MeSH terms: Antineoplastic Agents/pharmacokinetics; Taxoids/pharmacokinetics
  11. Enhancing biopharmaceutical performance of an anticancer drug by long chain PUFA based self-nanoemulsifying lipidic nanomicellar systems
    Khurana RK, Beg S, Burrow AJ, Vashishta RK, Katare OP, Kaur S, et al.
    Eur J Pharm Biopharm, 2017 Dec;121:42-60.
    PMID: 28887099 DOI: 10.1016/j.ejpb.2017.09.001
    The aim of this study was to develop polyunsaturated fatty acid (PUFA) long chain glyceride (LCG) enriched self-nanoemulsifying lipidic nanomicelles systems (SNELS) for augmenting lymphatic uptake and enhancing oral bioavailability of docetaxel and compare its biopharmaceutical performance with a medium-chain fatty acid glyceride (MCG) SNELS. Equilibrium solubility and pseudo ternary phase studies facilitated the selection of suitable LCG and MCG. The critical material attributes (CMAs) and critical process parameters (CPPs) were earmarked using Placket-Burman Design (PBD) and Fractional Factorial Design (FFD) for LCG- and MCG-SNELS respectively, and nano micelles were subsequently optimized using I- and D-optimal designs. Desirability function unearthed the optimized SNELS with Temul <5min, Dnm <100nm, Rel15min >85% and Perm45min >75%. The SNELS demonstrated efficient biocompatibility and energy dependent cellular uptake, reduced P-gp efflux and increased permeability using bi-directional Caco-2 model. Optimal PUFA enriched LCG-SNELS exhibited distinctly superior permeability and absorption parameters during ex vivo permeation, in situ single pass intestinal perfusion, lymphatic uptake and in vivo pharmacokinetic studies over MCG-SNELS.
    Matched MeSH terms: Antineoplastic Agents/pharmacokinetics*; Emulsions/pharmacokinetics*
  12. The Repurposing of Ivermectin for Malaria: A Prospective Pharmacokinetics-Based Virtual Clinical Trials Assessment of Dosing Regimen Options
    Badhan R, Zakaria Z, Olafuyi O
    J Pharm Sci, 2018 08;107(8):2236-2250.
    PMID: 29626533 DOI: 10.1016/j.xphs.2018.03.026
    Ivermectin has demonstrated many successes in the treatment of a range of nematode infections. Considering the increase in malaria resistance, attention has turned toward ivermectin as a candidate for repurposing for malaria. This study developed and validated an ivermectin physiology-based pharmacokinetic model in healthy adults (20-50 years), pediatric (3-5 years/15-25 kg) subjects, and a representative adult malaria population group (Thailand). Dosing optimization demonstrating a twice-daily dose for 3- or 5-day regimens would provide a time above the LC50 of more than 7 days for adult and pediatric subjects. Furthermore, to address the occurrence of CYP450 induction that is often encountered with antiretroviral agents, simulated drug-drug interaction studies with efavirenz highlighted that a 1-mg/kg once-daily dose for 5 days would counteract the increased ivermectin hepatic clearance and enable a time above LC50 of 138.8 h in adults and 141.2 h in pediatric subjects. It was also demonstrated that dosage regimen design would require consideration of the age-weight geographical relationship of the subjects, with a dosage regimen for a representative Thailand population group requiring at least a single daily dose for 5 days to maintain ivermectin plasma concentrations and a time above LC50 similar to that in healthy adults.
    Matched MeSH terms: Antiparasitic Agents/pharmacokinetics*; Ivermectin/pharmacokinetics*
  13. Fulltext pH-responsive Virus-like Nanoparticles with Enhanced Tumour-targeting Ligands for Cancer Drug Delivery
    Biabanikhankahdani R, Alitheen NBM, Ho KL, Tan WS
    Sci Rep, 2016 11 24;6:37891.
    PMID: 27883070 DOI: 10.1038/srep37891
    Multifunctional nanocarriers harbouring specific targeting moieties and with pH-responsive properties offer great potential for targeted cancer therapy. Several synthetic drug carriers have been studied extensively as drug delivery systems but not much information is available on the application of virus-like nanoparticles (VLNPs) as multifunctional nanocarriers. Here, we describe the development of pH-responsive VLNPs, based on truncated hepatitis B virus core antigen (tHBcAg), displaying folic acid (FA) for controlled drug delivery. FA was conjugated to a pentadecapeptide containing nanoglue bound on tHBcAg nanoparticles to increase the specificity and efficacy of the drug delivery system. The tHBcAg nanoparticles loaded with doxorubicin (DOX) and polyacrylic acid (PAA) demonstrated a sustained drug release profile in vitro under tumour tissue conditions in a controlled manner and improved the uptake of DOX in colorectal cancer cells, leading to enhanced antitumour effects. This study demonstrated that DOX-PAA can be packaged into VLNPs without any modification of the DOX molecules, preserving the pharmacological activity of the loaded DOX. The nanoglue can easily be used to display a tumour-targeting molecule on the exterior surface of VLNPs and can bypass the laborious and time-consuming genetic engineering approaches.
    Matched MeSH terms: Antibiotics, Antineoplastic/pharmacokinetics; Doxorubicin/pharmacokinetics
  14. Heavy metal quantification of classroom dust in school environment and its impacts on children health from Rawang (Malaysia)
    Tan SY, Praveena SM, Abidin EZ, Cheema MS
    Environ Sci Pollut Res Int, 2018 Dec;25(34):34623-34635.
    PMID: 30315534 DOI: 10.1007/s11356-018-3396-x
    This study aimed to determine bioavailable heavy metal concentrations (As, Cd, Co, Cu, Cr, Ni, Pb, Zn) and their potential sources in classroom dust collected from children's hand palms in Rawang (Malaysia). This study also aimed to determine the association between bioavailable heavy metal concentration in classroom dust and children's respiratory symptoms. Health risk assessment (HRA) was applied to evaluate health risks (non-carcinogenic and carcinogenic) due to heavy metals in classroom dust. The mean of bioavailable heavy metal concentrations in classroom dust found on children's hand palms was shown in the following order: Zn (1.25E + 01 μg/g) > Cu (9.59E-01 μg/g) > Ni (5.34E-01 μg/g) > Cr (4.72E-02 μg/g) > Co (2.34E-02 μg/g) > As (1.77E-02 μg/g) > Cd (9.60E-03 μg/g) > Pb (5.00E-03 μg/g). Hierarchical cluster analysis has clustered 17 sampling locations into three clusters, whereby cluster 1 (S3, S4, S6, S15) located in residential areas and near to roads exposed to vehicle emissions, cluster 2 (S10, S12, S9, S7) located near Rawang town and cluster 3 (S13, S16, S1, S2, S8, S14, S11, S17, S5) located near industrial, residential and plantation areas. Emissions from vehicles, plantations and industrial activities were found as the main sources of heavy metals in classroom dust in Rawang. There is no association found between bioavailable heavy metal concentrations and respiratory symptoms, except for Cu (OR = 0.03). Health risks (non-carcinogenic and carcinogenic risks) indicated that there are no potential non-carcinogenic and carcinogenic risks of heavy metals in classroom dust toward children health.
    Matched MeSH terms: Air Pollutants/pharmacokinetics; Metals, Heavy/pharmacokinetics
  15. Andrographolide is neither a human organic anion transporter 1 (hOAT1) substrate nor inhibitor
    Chong YM, Kaur G, Tan ML
    J Asian Nat Prod Res, 2019 Aug;21(8):754-771.
    PMID: 30606060 DOI: 10.1080/10286020.2018.1520704
    Andrographolide, a major bioactive compound isolated from Andrographis paniculata (Burm. F.) Nees, was evaluated for its effects on the hOAT1 membrane transporter. Substrate determination and inhibition of hOAT1-mediated uptake transport assay was carried out using recombinant CHO-hOAT1 cells. The results showed that the uptake ratio of andrographolide was less than 2.0 at all concentrations tested, indicating that andrographolide is not a hOAT1 substrate. Andrographolide has no significant effects on the p-aminohippuric acid uptake and on the mRNA and protein expression of hOAT1. In conclusion, andrographolide may not pose a drug-herb interaction risk related to hOAT1.
    Matched MeSH terms: Diterpenes/pharmacokinetics; p-Aminohippuric Acid/pharmacokinetics
  16. Fulltext Rabbit as an Animal Model for Pharmacokinetics Studies of Enteric Capsule Contains Recombinant Human Keratinocyte Growth Factor Loaded Chitosan Nanoparticles
    Kumar PV, Maki MAA, Wei YS, Tatt LM, Elumalai M, Cheah SC, et al.
    Curr Clin Pharmacol, 2019;14(2):132-140.
    PMID: 30457053 DOI: 10.2174/1574884714666181120103907
    BACKGROUND: Recombinant human keratinocyte growth factor (rHuKGF) has gained considerable attention by researchers as epithelial cells proliferating agent. Moreover, intravenous truncated rHuKGF (palifermin) has been approved by Food and Drug Administration (FDA) to treat and prevent chemotherapy-induced oral mucositis and small intestine ulceration. The labile structure and short circulation time of rHuKGF in-vivo are the main obstacles that reduce the oral bioactivity and dosage of such proteins at the target site.

    OBJECTIVE: Formulation of methacrylic acid-methyl methacrylate copolymer-coated capsules filled with chitosan nanoparticles loaded with rHuKGF for oral delivery.

    METHODS: We report on chitosan nanoparticles (CNPs) with diameter < 200 nm, prepared by ionic gelation, loaded with rHuKGF and filled in methacrylic acid-methyl methacrylate copolymercoated capsules for oral delivery. The pharmacokinetic parameters were determined based on the serum levels of rHuKGF, following a single intravenous (IV) or oral dosages using a rabbit model. Furthermore, fluorescent microscope imaging was conducted to investigate the cellular uptake of the rhodamine-labelled rHuKGF-loaded nanoparticles. The proliferation effect of the formulation on FHs 74 Int cells was studied as well by MTT assay.

    RESULTS: The mucoadhesive and absorption enhancement properties of chitosan and the protective effect of methacrylic acid-methyl methacrylate copolymer against rHuKGF release at the stomach, low pH, were combined to promote and ensure rHuKGF intestinal delivery and increase serum levels of rHuKGF. In addition, in-vitro studies revealed the protein bioactivity since rHuKGFloaded CNPs significantly increased the proliferation of FHs 74 Int cells.

    CONCLUSION: The study revealed that oral administration of rHuKGF-loaded CNPs in methacrylic acid-methyl methacrylate copolymer-coated capsules is practically alternative to the IV administration since the absolute bioavailability of the orally administered rHuKGF-loaded CNPs, using the rabbit as animal model, was 69%. Fluorescent microscope imaging revealed that rhodaminelabelled rHuKGF-loaded CNPs were taken up by FHs 74 Int cells, after 6 hours' incubation time, followed by increase in the proliferation rate.

    Matched MeSH terms: Recombinant Proteins/pharmacokinetics; Fibroblast Growth Factor 7/pharmacokinetics*
  17. Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn's disease in Asia
    Ooi CJ, Hilmi I, Banerjee R, Chuah SW, Ng SC, Wei SC, et al.
    J Gastroenterol Hepatol, 2019 Aug;34(8):1296-1315.
    PMID: 30848854 DOI: 10.1111/jgh.14648
    The Asia-Pacific Working Group on Inflammatory Bowel Disease was established in Cebu, Philippines, under the auspices of the Asia-Pacific Association of Gastroenterology with the goal of improving inflammatory bowel disease care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn's and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in conjunction with conventional treatments for ulcerative colitis and Crohn's disease in Asia. These statements also address how pharmacogenetics influences the treatments of ulcerative colitis and Crohn's disease and provides guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of inflammatory bowel disease workgroup employing the modified Delphi process. These statements do not intend to be all-encompassing, and future revisions are likely as new data continue to emerge.
    Matched MeSH terms: Biological Products/pharmacokinetics; Immunologic Factors/pharmacokinetics
  18. Fulltext A balanced randomised placebo controlled blinded phase IIa multi-centre study to investigate the efficacy and safety of AUT00063 versus placebo in subjective tinnitus: The QUIET-1 trial
    Hall DA, Ray J, Watson J, Sharman A, Hutchison J, Harris P, et al.
    Hear Res, 2019 06;377:153-166.
    PMID: 30939361 DOI: 10.1016/j.heares.2019.03.018
    AUT00063 is an experimental new medicine that has been demonstrated to suppress spontaneous hyperactivity by modulating the action of voltage-gated potassium-channels in central auditory cortical neurons of a rodent model. This neurobiological property makes it a good candidate for treating the central component of subjective tinnitus but this has not yet been tested in humans. The main purpose of the QUIET-1 (QUest In Eliminating Tinnitus) trial was to examine the effect of AUT00063 on the severity of tinnitus symptoms in people with subjective tinnitus. The trial was a randomised, placebo-controlled, observer, physician and participant blinded multi-centre superiority trial with two parallel groups and a primary endpoint of functional impact on tinnitus 28 days after the first drug dosing day. The trial design overcame the scale and logistical challenges of delivering a scientifically robust, statistically powered multi-centre study for subjective tinnitus within the National Health Service in England. The trial was terminated early for futility. Overall, 212 participants consented across 18 sites with 91 participants randomised to groups using age, gender, tinnitus symptom severity and hearing status as minimisation factors. While the pharmacokinetic markers confirm the uptake of AUT00063 in the body, within the expected therapeutic range, with respect to clinical benefit findings indicated that AUT00063 was not effective in alleviating tinnitus symptoms (1.56 point change in Tinnitus Functional Index). In terms of clinical harms, results indicated that a daily dose of 800 mg capsules of AUT00063 taken for 28 days was safe and well tolerated. These findings provide significant advances in the drug development field for hearing sciences, but raise questions about the predictive validity of certain rodent models of noise-induced hearing loss and tinnitus, as least for the mechanism evaluated in the present study. Trial Registration: (EudraCT) 2014-002179-27; NCT02315508.
    Matched MeSH terms: Imidazoles/pharmacokinetics; Pyrimidines/pharmacokinetics
  19. Health risk assessment of heavy metal accumulation in the Buriganga and Turag River systems for Puntius ticto, Heteropneustes fossilis, and Channa punctatus
    Baki MA, Shojib MFH, Sehrin S, Chakraborty S, Choudhury TR, Bristy MS, et al.
    Environ Geochem Health, 2020 Feb;42(2):531-543.
    PMID: 31376046 DOI: 10.1007/s10653-019-00386-4
    This study aimed to assess the effects of major ecotoxic heavy metals accumulated in the Buriganga and Turag River systems on the liver, kidney, intestine, and muscle of common edible fish species Puntius ticto, Heteropneustes fossilis, and Channa punctatus and determine the associated health risks. K was the predominant and reported as a major element. A large concentration of Zn was detected in diverse organs of the three edible fishes compared with other metals. Overall, trace metal analysis indicated that all organs (especially the liver and kidney) were under extreme threat because the maximum permissible limit set by different international health organizations was exceeded. The target hazard quotient and target cancer risk due to the trace metal content were the largest for P. ticto. Thus, excessive intake of P. ticto from the rivers Buriganga and Turag could result in chronic risks associated with long-term exposure to contaminants. Histopathological investigations revealed the first detectable indicators of infection and findings of long-term injury in cells, tissues, and organs. Histopathological changes in various tissue structures of fish functioned as key pointers of connection to pollutants, and definite infections and lesion types were established based on biotic pointers of toxic/carcinogenic effects. The analysis of histopathological alterations is a controlling integrative device used to assess pollutants in the environment.
    Matched MeSH terms: Water Pollutants, Chemical/pharmacokinetics; Metals, Heavy/pharmacokinetics
  20. Defining a threshold for tacrolimus intra-patient variability associated with late acute cellular rejection in paediatric kidney transplant recipients
    Abu Bakar K, Mohamad NA, Hodi Z, McCulloch T, Williams A, Christian M, et al.
    Pediatr Nephrol, 2019 12;34(12):2557-2562.
    PMID: 31520127 DOI: 10.1007/s00467-019-04346-z
    BACKGROUND: Late acute cellular rejection (LACR) is associated with poorer graft outcomes and non-adherence. Non-adherence to tacrolimus can be indirectly assessed by the intra-patient variability (IPV) of tacrolimus trough levels. The threshold of IPV associated with rejection is not known.

    METHODS: We conducted a case-control study comparing 25 patients with biopsy-proven LACR against 25 stable controls matched for age group, primary diagnosis and time post-transplant. IPV was calculated using coefficient of variance (CV) and mean absolute deviation (MAD) using tacrolimus levels in the preceding 12 months. We also assessed the percentage time for tacrolimus levels

    Matched MeSH terms: Immunosuppressive Agents/pharmacokinetics; Tacrolimus/pharmacokinetics
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