Displaying publications 1 - 20 of 505 in total

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  1. Leong SW, Abas F, Lam KW, Shaari K, Lajis NH
    Bioorg Med Chem, 2016 08 15;24(16):3742-51.
    PMID: 27328658 DOI: 10.1016/j.bmc.2016.06.016
    In the present study, a series of 2-benzoyl-6-benzylidenecyclohexanone analogs have been synthesized and evaluated for their anti-cholinesterase activity. Among the forty-one analogs, four compounds (38, 39, 40 and 41) have been identified as lead compounds due to their highest inhibition on both AChE and BChE activities. Compounds 39 and 40 in particular exhibited highest inhibition on both AChE and BChE with IC50 values of 1.6μM and 0.6μM, respectively. Further structure-activity relationship study suggested that presence of a long-chain heterocyclic in one of the rings played a critical role in the dual enzymes' inhibition. The Lineweaver-Burk plots and docking results suggest that both compounds could simultaneously bind to the PAS and CAS regions of the enzyme. ADMET analysis further confirmed the therapeutic potential of both compounds based upon their high BBB-penetrating. Thus, 2-benzoyl-6-benzylidenecyclohexanone containing long-chain heterocyclic amine analogs represent a new class of cholinesterase inhibitor, which deserve further investigation for their development into therapeutic agents for cognitive diseases such as Alzheimer.
    Matched MeSH terms: Cholinesterase Inhibitors/pharmacokinetics
  2. Khan NR, Wong TW
    Artif Cells Nanomed Biotechnol, 2018;46(sup1):568-577.
    PMID: 29378453 DOI: 10.1080/21691401.2018.1431650
    This study focuses on the use of ethosome and microwave technologies to facilitate skin penetration and/or deposition of 5-fluorouracil in vitro and in vivo. Low ethanol ethosomes were designed and processed by mechanical dispersion technique and had their size, zeta potential, morphology, drug content and encapsulation efficiency characterized. The skin was pre-treated with microwave at 2450 MHz for 2.5 min with ethosomes applied topically and subjected to in vitro and in vivo skin drug permeation as well as retention evaluation. The drug and/or ethosomes cytotoxicity, uptake and intracellular trafficking by SKMEL-28 melanoma cell culture were evaluated. Pre-treatment of skin by microwave promoted significant drug deposition in skin from ethosomes in vitro while keeping the level of drug permeation unaffected. Similar observations were obtained in vivo with reduced drug permeation into blood. Combination ethosome and microwave technologies enhanced intracellular localization of ethosomes through fluidization of cell membrane lipidic components as well as facilitating endocytosis by means of clathrin, macropinocytosis and in particularly lipid rafts pathways. The synergistic use of microwave and ethosomes opens a new horizon for skin malignant melanoma treatment.
    Matched MeSH terms: Fluorouracil/pharmacokinetics
  3. Ahmad Fuzi SF, Koller D, Bruggraber S, Pereira DI, Dainty JR, Mushtaq S
    Am J Clin Nutr, 2017 Dec;106(6):1413-1421.
    PMID: 29046302 DOI: 10.3945/ajcn.117.161364
    Background: Tea has been shown to be a potent inhibitor of nonheme iron absorption, but it remains unclear whether the timing of tea consumption relative to a meal influences iron bioavailability.Objective: The aim of the study was to investigate the effect of a 1-h time interval of tea consumption on nonheme iron absorption in an iron-containing meal in a cohort of iron-replete, nonanemic female subjects with the use of a stable isotope (57Fe).Design: Twelve women (mean ± SD age: 24.8 ± 6.9 y) were administered a standardized porridge meal extrinsically labeled with 4 mg 57Fe as FeSO4 on 3 separate occasions, with a 14-d time interval between each test meal (TM). The TM was administered with water (TM-1), with tea administered simultaneously (TM-2), and with tea administered 1 h postmeal (TM-3). Fasted venous blood samples were collected for iron isotopic analysis and measurement of iron status biomarkers. Fractional iron absorption was estimated by the erythrocyte iron incorporation method.Results: Iron absorption was 5.7% ± 8.5% (TM-1), 3.6% ± 4.2% (TM-2), and 5.7% ± 5.4% (TM-3). Mean fractional iron absorption was found to be significantly higher (2.2%) when tea was administered 1 h postmeal (TM-3) than when tea was administered simultaneously with the meal (TM-2) (P = 0.046). An ∼50% reduction in the inhibitory effect of tea (relative to water) was observed, from 37.2% (TM-2) to 18.1% (TM-3).Conclusions: This study shows that tea consumed simultaneously with an iron-containing porridge meal leads to decreased nonheme iron absorption and that a 1-h time interval between a meal and tea consumption attenuates the inhibitory effect, resulting in increased nonheme iron absorption. These findings are not only important in relation to the management of iron deficiency but should also inform dietary advice, especially that given to those at risk of deficiency. This trial was registered at clinicaltrials.gov as NCT02365103.
    Matched MeSH terms: Iron/pharmacokinetics*; Iron Isotopes/pharmacokinetics; Iron, Dietary/pharmacokinetics*
  4. Eich A, Urban V, Jutel M, Vlcek J, Shim JJ, Trofimov VI, et al.
    COPD, 2017 Oct;14(5):476-483.
    PMID: 28753067 DOI: 10.1080/15412555.2017.1335697
    Interleukin (IL)-17A may be an underlying factor in the pathophysiology of chronic obstructive pulmonary disease (COPD). Anti-IL-17 monoclonal antibodies have been used successfully in treating several immune-mediated inflammatory diseases. This phase 2, randomized, placebo-controlled, double-blind, parallel-group, proof-of-concept study is the first clinical study evaluating the efficacy and safety of the anti-IL-17A monoclonal antibody CNTO 6785 in patients with symptomatic moderate-to-severe COPD. Patients were treated with CNTO 6785 (n = 93) or placebo (n = 94) intravenously at Weeks 0, 2, and 4 (induction), then Weeks 8 and 12, and followed till Week 24. The primary efficacy endpoint was the change from baseline in pre-bronchodilator percent-predicted forced expiratory volume in 1 second at Week 16. Samples were collected at all visits for pharmacokinetic (PK) evaluation, and standard safety assessments were performed. The mean difference in the primary efficacy endpoint between CNTO 6785 and placebo was not statistically significant (-0.49%; p = 0.599). No other efficacy endpoints demonstrated clinically or statistically significant differences with CNTO 6785 compared with placebo. CNTO 6785 was generally well tolerated; no major safety signals were detected. The most frequently reported treatment-emergent adverse events were infections and infestations; however, no notable differences were observed between CNTO 6785 and placebo in terms of rates of infections. PK results suggested that the steady state of serum CNTO 6785 concentration was reached within 16 weeks. These results suggest that IL-17A is unlikely to be a dominant driver in the pathology of, or a viable therapeutic target for, COPD. ClinicalTrials.gov Identifier: NCT01966549; EudraCT Identifier: 2012-003607-36.
    Matched MeSH terms: Antibodies, Monoclonal/pharmacokinetics
  5. 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
  6. Chik Z, Basu RC, Pendek R, Lee TC, Mohamed Z
    Clin Ther, 2010 Sep;32(10):1822-31.
    PMID: 21194606 DOI: 10.1016/j.clinthera.2010.09.006
    Rifampicin is a semisynthetic antibiotic derivative of rifamycin used worldwide for the treatment of various forms of tuberculosis.
    Matched MeSH terms: Antibiotics, Antitubercular/pharmacokinetics*; Rifampin/pharmacokinetics*
  7. Hong Ng C, Norman TR, Naing KO, Schweitzer I, Kong Wai Ho B, Fan A, et al.
    Int Clin Psychopharmacol, 2006 Mar;21(2):87-92.
    PMID: 16421459
    This prospective 6-week study examined the differences in dosage and steady state plasma concentrations of sertraline in Chinese versus Caucasian depressed patients. Two groups of Chinese patients from different geographical sites and a group of Caucasian patients were evaluated with clinical measures during an initial dose of 50 mg/day, with subsequent doses adjusted clinically. The results of 17 Australian Chinese (ACHI), 13 Malaysian Chinese (MCHI) and 15 Australian Caucasians (AC) were analysed. Despite controlling for weight, the AC subjects received a significantly higher dose than both the ACHI (P = 0.002) and the MCHI groups (P = 0.012). However, the mean sertraline concentration to dose ratios at weeks 1 and 6 were not significantly different between the three groups. Sertraline was effective and well tolerated in both ethnic groups with few adverse events. Although there was a lack of difference between groups in the pharmacokinetic results, Chinese depressed patients appeared to require lower dosages with consequently lower plasma concentrations of sertraline compared to Caucasian patients to achieve clinical efficacy. Further studies of the dosages, kinetics and adverse effects of selective serotonin reuptake inhibitors linked with genotyping are necessary.
    Matched MeSH terms: Antidepressive Agents/pharmacokinetics*; Sertraline/pharmacokinetics*
  8. Tan NH, Armugam A, Tan CS
    Comp. Biochem. Physiol., B, 1989;93(4):757-62.
    PMID: 2553329
    1. The lethalities, anticoagulant effects, hermorrhagic, thrombin-like enzyme, hyaluronidase, protease, arginine ester hydrolase, 5'-nucleotidase, L-amino acid oxidase, alkaline phosphomonoesterase, phosphodiesterase and phospholipase A activities of twenty-three samples of venoms from twelve species of Asian lance-headed pit vipers (genus Trimeresurus) were examined. 2. The results indicate that notwithstanding individual variations in venom properties, the differences in biological properties of the Trimeresurus venoms can be used for the differentiation of venoms from different species of Trimeresurus. 3. The results also suggest that differences in the biological properties of snake venoms are useful parameters in the classification of snake species. 4. Our results indicate that venoms from the species T. okinavensis exhibited biological properties markedly different from other Trimeresurus venoms examined. This observation supports the recently proposed reclassification of T. okinavensis as a member of the genus Ovophis, rather than the genus Trimeresurus.
    Matched MeSH terms: Crotalid Venoms/pharmacokinetics
  9. Tasnim J, Hashim NM, Han HC
    Cell Biochem Funct, 2024 Mar;42(2):e3967.
    PMID: 38480622 DOI: 10.1002/cbf.3967
    A drug interaction is a condition in which two or more drugs are taken at the same time. Type 2 diabetes mellitus is a significant contributor to polypharmacy. Proton pump inhibitors (PPIs) are often prescribed in combination with metformin or DPP-4 inhibitors (sitagliptin, saxagliptin, linagliptin, and alogliptin) or a combined dose of metformin and DPP-4 inhibitor to treat gastritis in diabetic patients. This review article mainly focused on evaluating the potential drug-drug interactions (DDIs) between PPIs (i.e. esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole) with metformin and PPIs with DPP-4 inhibitors. The findings demonstrated the existence of pharmacokinetic and pharmacodynamic DDIs between the aforementioned PPIs with metformin and DPP-4 inhibitors, which could impact the biological activities (i.e., hypoglycemia) of these drugs. Moreover, this review suggested that esomeprazole could be the best drug in the PPI group to be prescribed simultaneously with metformin and DPP-4 inhibitors, as most of the antidiabetic drugs of this study did not show any interaction with esomeprazole. The findings of this study also revealed that both antidiabetic drugs and PPIs could have positive interactions as PPIs have the potential to lessen the gastrointestinal side effects of metformin and DPP-4 inhibitors. To achieve the greatest therapeutic impact with the fewest side effects, careful dose control of these drugs is required. So, more extensive research on both human and animal subjects are needed to ascertain the veracity of this hypothesis.
    Matched MeSH terms: Proton Pump Inhibitors/pharmacokinetics
  10. Amekyeh H, Billa N, Yuen KH, Chin SL
    AAPS PharmSciTech, 2015 Aug;16(4):871-7.
    PMID: 25588365 DOI: 10.1208/s12249-014-0279-4
    The gastrointestinal (GI) transit behavior of and absorption from an amphotericin B (AmB) solid lipid nanoformulation (SLN) in rats was investigated. We aimed to estimate the gastric emptying time (GET) and cecal arrival time (CAT) of AmB SLN in rats as animal models. From these two parameters, an insight on the absorption window of AmB was ascertained. Three types of SLNs, AmB, paracetamol (PAR), and sulfasalazine (SSZ), were similarly formulated using beeswax/theobroma oil composite as the lipid matrix and characterized with regard to size, viscosity, density, migration propensity within agarose gel, in vitro drug release, morphology, gastrointestinal transit, and in vivo absorption. The GET and CAT were estimated indirectly using marker drugs: PAR and sulfapyridine (SP). All three types of SLNs exhibited identical properties with regard to z-average, viscosity, relative density, and propensity to migrate. PAR was absorbed rapidly from the small intestine following emptying of the SLNs giving the T50E (time for 50% absorption of PAR) to be 1.6 h. SP was absorbed after release and microbial degradation of SSZ from SLN in the colon with a lag time of 2 h post-administration, serving as the estimated cecal arrival time of the SLNs. AmB within SLN was favorably absorbed from the small intestine, albeit slowly.
    Matched MeSH terms: Acetaminophen/pharmacokinetics; Amphotericin B/pharmacokinetics*; Sulfasalazine/pharmacokinetics
  11. Chan KL, Yuen KH, Jinadasa S, Peh KK, Toh WT
    Planta Med, 1997 Feb;63(1):66-9.
    PMID: 9063097
    A high-performance liquid chromatography assay equipped with a glassy carbon electrode for electrochemical detection (HPLC-ECD) was developed at reductive mode for the analysis of artemisinin, the antimalarial drug from Artemisia annua (Asteraceae) in human plasma. This method was selective, sensitive, and produced satisfactory recovery, precision, and accuracy. Analysis of plasma samples from 8 male volunteers given 10 mg kg-1 of artemisinin orally as an aqueous suspension showed a mean peak plasma concentration (Cmax) of 580.89 ng ml-1 +/- 88.64 SD at 2.5 h +/- 0.5 SD after dosing, and the mean area under the plasma concentration-time curve (AUC0-infinity) was 2227.57 ng h ml-1 +/- 677.22 SD. In addition, the elimination rate constant (Ke), elimination half-life (t1/2), and apparent volume of distribution (Vd) were calculated to be 0.2971 h-1 +/- 0.0644 SD, 2.42 h +/- 0.46 SD, and 16.26 l kg-1 +/- 3.44 SD, respectively.
    Matched MeSH terms: Antimalarials/pharmacokinetics; Sesquiterpenes/pharmacokinetics
  12. Dear JW, Ng ML, Bateman DN, Leroy Sivappiragasam P, Choi H, Khoo BBJ, et al.
    Clin Transl Sci, 2021 07;14(4):1476-1489.
    PMID: 33742775 DOI: 10.1111/cts.13009
    N-acetylcysteine (NAC) is an antidote to prevent acetaminophen (paracetamol-APAP)-induced acute liver injury (ALI). The 3-bag licensed 20.25 h standard regimen, and a 12 h modified regimen, are used to treat APAP overdose. This study evaluated the redox thiol response and APAP metabolites, in patients with a single APAP overdose treated with either the 20.25 h standard or 12 h modified regimen. We used liquid chromatography tandem mass spectrometry to quantify clinically important oxidative stress biomarkers and APAP metabolites in plasma samples from 45 patients who participated in a randomized controlled trial (SNAP trial). We investigated the time course response of plasma metabolites at predose, 12 h, and 20.25 h post-start of NAC infusion. The results showed that the 12 h modified regimen resulted in a significant elevation of plasma NAC and cysteine concentrations at 12 h post-infusion. We found no significant alteration in the metabolism of APAP, mitochondrial, amino acids, and other thiol biomarkers with the two regimens. We examined APAP and purine metabolism in overdose patients who developed ALI. We showed the major APAP-metabolites and xanthine were significantly higher in patients with ALI. These biomarkers correlated well with alanine aminotransferase activity at admission. Receiver operating characteristic analysis showed that at admission, plasma APAP-metabolites and xanthine concentrations were predictive for ALI. In conclusion, a significantly higher redox thiol response with the modified NAC regimen at 12 h postdose suggests this regimen may produce greater antioxidant efficacy. At baseline, plasma APAP and purine metabolites may be useful biomarkers for early prediction of APAP-induced ALI.
    Matched MeSH terms: Acetaminophen/pharmacokinetics
  13. Tanvir EM, Afroz R, Chowdhury M, Gan SH, Karim N, Islam MN, et al.
    Hum Exp Toxicol, 2016 Sep;35(9):991-1004.
    PMID: 26519480 DOI: 10.1177/0960327115614384
    This study investigated the main target sites of chlorpyrifos (CPF), its effect on biochemical indices, and the pathological changes observed in rat liver and kidney function using gas chromatography/mass spectrometry. Adult female Wistar rats (n = 12) were randomly assigned into two groups (one control and one test group; n = 6 each). The test group received CPF via oral gavage for 21 days at 5 mg/kg daily. The distribution of CPF was determined in various organs (liver, brain, heart, lung, kidney, ovary, adipose tissue, and skeletal muscle), urine and stool samples using GCMS. Approximately 6.18% of CPF was distributed in the body tissues, and the highest CPF concentration (3.80%) was found in adipose tissue. CPF also accumulated in the liver (0.29%), brain (0.22%), kidney (0.10%), and ovary (0.03%). Approximately 83.60% of CPF was detected in the urine. CPF exposure resulted in a significant increase in plasma transaminases, alkaline phosphatase, and total bilirubin levels, a significant reduction in total protein levels and an altered lipid profile. Oxidative stress due to CPF administration was also evidenced by a significant increase in liver malondialdehyde levels. The detrimental effects of CPF on kidney function consisted of a significant increase in plasma urea and creatinine levels. Liver and kidney histology confirmed the observed biochemical changes. In conclusion, CPF bioaccumulates over time and exerts toxic effects on animals.
    Matched MeSH terms: Chlorpyrifos/pharmacokinetics; Environmental Pollutants/pharmacokinetics
  14. Ramanathan S, Karupiah S, Nair NK, Olliaro PL, Navaratnam V, Wernsdorfer WH, et al.
    PMID: 16046285
    A new approach using a simple solid-phase extraction technique has been developed for the determination of pyronaridine (PND), an antimalarial drug, in human plasma. After extraction with C18 solid-phase sorbent, PND was analyzed using a reverse phase chromatographic method with fluorescence detection (at lambda(ex)=267 nm and lambda(em)=443 nm). The mean extraction recovery for PND was 95.2%. The coefficient of variation for intra-assay precision, inter-assay precision and accuracy was less than 10%. The quantification limit with fluorescence detection was 0.010 microg/mL plasma. The method described herein has several advantages over other published methods since it is easy to perform and rapid. It also permits reducing both, solvent use and sample preparation time. The method has been used successfully to assay plasma samples from clinical pharmacokinetic studies.
    Matched MeSH terms: Antimalarials/pharmacokinetics; Naphthyridines/pharmacokinetics
  15. Kumaresan V, Bhatt P, Ganesh MR, Harikrishnan R, Arasu M, Al-Dhabi NA, et al.
    Mol Immunol, 2015 Dec;68(2 Pt B):421-33.
    PMID: 26477736 DOI: 10.1016/j.molimm.2015.10.001
    In aquaculture, accumulation of antibiotics resulted in development of resistance among bacterial pathogens. Consequently, it became mandatory to find alternative to synthetic antibiotics. Antimicrobial peptides (AMPs) which are described as evolutionary ancient weapons have been considered as promising alternates in recent years. In this study, a novel antimicrobial peptide had been derived from goose type lysozyme (LyzG) which was identified from the cDNA library of freshwater fish Channa striatus (Cs). The identified lysozyme cDNA contains 585 nucleotides which encodes a protein of 194 amino acids. CsLyzG was closely related to Siniperca chuatsi with 92.8% homology. The depicted protein sequence contained a GEWL domain with conserved GLMQ motif, 7 active residues and 2 catalytic residues. Gene expression analysis revealed that CsLyzG was distributed in major immune organs with highest expression in head kidney. Results of temporal expression analysis after bacterial (Aeromonas hydrophila) and fungal (Aphanomyces invadans) challenges indicated a stimulant-dependent expression pattern of CsLyzG. Two antimicrobial peptides IK12 and TS10 were identified from CsLyzG and synthesized. Antibiogram showed that IK12 was active against Salmonella enterica, a major multi-drug resistant (MDR) bacterial pathogen which produces beta lactamase. The IK12 induced loss of cell viability in the bacterial pathogen. Flow cytometry assay revealed that IK12 disrupt the membrane of S. enterica which is confirmed by scanning electron microscope (SEM) analysis that reveals blebs around the bacterial cell membrane. Conclusively, CsLyzG is a potential innate immune component and the identified antimicrobial peptide has great caliber to be used as an ecofriendly antibacterial substance in aquaculture.
    Matched MeSH terms: Anti-Infective Agents/pharmacokinetics; Muramidase/pharmacokinetics; Antimicrobial Cationic Peptides/pharmacokinetics; Fish Proteins/pharmacokinetics
  16. Cheah KY, Mah KY, Pang LH, Ng SM, Wong JW, Tan SS, et al.
    BMC Pharmacol Toxicol, 2020 06 23;21(1):45.
    PMID: 32576287 DOI: 10.1186/s40360-020-00416-3
    BACKGROUND: Paracetamol/Orphenadrine is a fixed dose combination containing 35 mg orphenadrine and 450 mg paracetamol. It has analgesic and muscle relaxant properties and is widely available as generics. This study is conducted to investigate the relative bioavailability and bioequivalence between one fixed dose paracetamol/orphenadrine combination test preparation and one fixed dose paracetamol/orphenadrine combination reference preparation in healthy volunteers under fasted condition for marketing authorization in Malaysia.

    METHOD: This is a single-center, single-dose, open-label, randomized, 2-treatment, 2-sequence and 2-period crossover study with a washout period of 7 days. Paracetamol/Orphenadrine tablets were administered after a 10-h fast. Blood samples for pharmacokinetic analysis were collected at scheduled time intervals prior to and up to 72 h after dosing. Blood samples were centrifuged, and separated plasma were kept frozen (- 15 °C to - 25 °C) until analysis. Plasma concentrations of orphenadrine and paracetamol were quantified using liquid-chromatography-tandem mass spectrometer using diphenhydramine as internal standard. The pharmacokinetic parameters AUC0-∞, AUC0-t and Cmax were determined using plasma concentration time profile for both preparations. Bioequivalence was assessed according to the ASEAN guideline acceptance criteria for bioequivalence which is the 90% confidence intervals of AUC0-∞, AUC0-t and Cmax ratio must be within the range of 80.00-125.00%.

    RESULTS: There were 28 healthy subjects enrolled, and 27 subjects completed this trial. There were no significant differences observed between the AUC0-∞, AUC0-t and Cmax of both test and reference preparations in fasted condition. The 90% confidence intervals for the ratio of AUC0-t (100.92-111.27%), AUC0-∞ (96.94-108.08%) and Cmax (100.11-112.50%) for orphenadrine (n = 25); and AUC0-t (94.29-101.83%), AUC0-∞ (94.77-101.68%) and Cmax (87.12-101.20%) for paracetamol (n = 27) for test preparation over reference preparation were all within acceptable bioequivalence range of 80.00-125.00%.

    CONCLUSION: The test preparation is bioequivalent to the reference preparation and can be used interchangeably.

    TRIAL REGISTRATION: NMRR- 17-1266-36,001; registered and approved on 12 September 2017.

    Matched MeSH terms: Acetaminophen/pharmacokinetics*; Muscle Relaxants, Central/pharmacokinetics*; Orphenadrine/pharmacokinetics*; Analgesics, Non-Narcotic/pharmacokinetics*
  17. Chin KY, Mo H, Soelaiman IN
    Curr Drug Targets, 2013 Dec;14(13):1533-41.
    PMID: 23859472
    Osteoporosis is posing a tremendous healthcare problem globally. Much effort has been invested in finding novel antiosteoporotic agents to stop the progression of this disease. Tocotrienol, one of the isoforms of vitamin E, is poised as a potential antiosteoporotic agent. Previous studies showed that tocotrienol as a single isomer or as a mixture demonstrated both anabolic and antiresorptive effects in various rodent models of osteoporosis. In vitro experiments further demonstrated that tocotrienol could up-regulate genes related to osteoblastogenesis and modify receptor activator of nuclear factor kappa B signaling against osteoclastogenesis. Additionally, tocotrienol was also shown to be a strong 3- hydroxy-3-methyl-glutaryl-CoA reductase down-regulator with a mechanism different from that of statins. Inhibition of the mevalonate pathway affects both osteoblast and osteoclast formation in favor of the former. Tocopherol, a more commonly used isoform of vitamin E does not possess similar effects. Tocotrienol is also a potent antioxidant. It can scavenge free radicals and prevent oxidative damage on osteoblast thus promoting its survival. It may also up-regulate the antioxidant defense network in osteoclast and indirectly act against free radical signaling essential in osteoclastogenesis. The effects of tocotrienol on Wnt/β-catenin signaling essential in osteoblastogenesis have not been determined. More mechanistic studies need to be conducted to illustrate the antiosteoporotic effects of tocotrienol. Clinical trials are also required to confirm its effects in humans. In conclusion, tocotrienol demonstrates great potential as an antiosteoporotic agent and much research effort should be invested to develop it as an agent to curb osteoporosis.
    Matched MeSH terms: Tocopherols/pharmacokinetics
  18. Abdul-Majeed S, Mohamed N, Soelaiman IN
    Curr Drug Targets, 2013 Dec;14(13):1579-90.
    PMID: 23848479
    Skeletal tissue undergoes continuous remodeling which makes it unique among other body tissues. Osteoporosis is a common bone metabolic disorder affecting both men and women. Osteoporosis and its complications mainly osteoporotic fractures, have a high impact on health and economy. Current approved medications are associated with numerous side effects, which limit their use. Identification of a new and safe therapy is mandatory. Statins, also known as HMGCoA reductase inhibitors, are frequently used for the treatment of hypercholesterolemia and for the prevention of morbidity and mortality associated with cardiovascular disease. Statins improved bone health status in intact and ovariectomised rodents following high clinically intolerable oral doses. However, this beneficial effect of statins could not be significantly demonstrated in humans. The reason behind this discrepancy might be due to the safety and bioavailability of the currently used oral statins. Vitamin E, especially the tocotrienols at the dose 60 mg/kg/day provided significant antiosteoporotic effects in different animal models of osteoporosis. The use of the aforementioned dose of tocotrienols was shown to be safe in both humans and animals. Enhancement of bone formation and reduction of bone resorption were achieved more effectively by a combination of tocotrienols and statins than by either treatment when supplemented separately at clinically tolerable doses. Therefore, the adverse effects associated with high statin doses might be avoided with the coadministration of tocotrienols. Moreover, the combination therapy strategy might be useful for patients who are at high risk of osteoporosis, cardiovascular events and hypercholesterolaemia.
    Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacokinetics; Tocotrienols/pharmacokinetics
  19. Gumel AB, Kubota K, Twizell EH
    Math Biosci, 1998 Aug 15;152(1):87-103.
    PMID: 9727298
    A sequential algorithm is developed for the non-linear dual-sorption model developed by Chandrasekaran et al. [1,2] which monitors pharmacokinetic profiles in percutaneous drug absorption. In the experimental study of percutaneous absorption, it is often observed that the lag-time decreases with the increase in the donor concentration when two or more donor concentrations of the same compound are used. The dual-sorption model has sometimes been employed to explain such experimental results. In this paper, it is shown that another feature observed after vehicle removal may also characterize the dual-sorption model. Soon after vehicle removal, the plots of the drug flux versus time become straight lines on a semilogarithmic scale as in the linear model, but the half-life is prolonged thereafter when the dual-sorption model prevails. The initial half-life after vehicle removal with a low donor concentration is longer than that with a higher donor concentration. These features, if observed in experiments, may be used as evidence to confirm that the dual-sorption model gives an explanation to the non-linear kinetic behaviour of a permeant.
    Matched MeSH terms: Pharmacokinetics
  20. Ali HS, Khan S, York P, Shah SM, Khan J, Hussain Z, et al.
    Pak J Pharm Sci, 2017 Sep;30(5):1635-1643.
    PMID: 29084684
    Drug nanosuspensions have gained tremendous attraction as a platform in drug delivery. In the present work, a nanosuspension was prepared by a wet milling approach in order to increase saturation solubility and dissolution of the water insoluble drug, hydrocortisone. Size of the generated particeles was 290 nm ± 9 nm having a zeta potential of -1.9 mV ± 0.6 mV. Nanosized particles were found to have a rod shape with a narrow particle size distribution (PDI =0.17). Results of differential scanning calorimetry and X-ray diffraction analyses revealed minor modifications of crystallinity of hydrocortisone following the milling process. Solubility of hydrocortisone was enhanced by nanonization to 875µg/ml ±2.5, an almost 2.9-fold compared to the raw hydrocortisone. Moreover, the nanosuspension formulation substabtially enhanced the dissolution rate of hydrocortisone where >97% of the hydrocortisone was dissolved within 10 minutes opposed to 22.3% for the raw 50% for the raw hydrocortisone and the commercial tablet, respectively. The bioavailability study resulted in AUC 0-9h for HC nanosuspensions (31.50±2.50), which is significantly (p<0.05) higher compared to the AUC 0-9h (14.85±3.25) resulted for HC solution. The nanosuspension was physically stable at room temperature for 24 months.
    Matched MeSH terms: Hydrocortisone/pharmacokinetics
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