Displaying publications 21 - 40 of 276 in total

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  1. Fulltext Pharmacokinetics of a novel sublingual spray formulation of the antimalarial drug artemether in healthy adults
    Salman S, Bendel D, Lee TC, Templeton D, Davis TM
    Antimicrob Agents Chemother, 2015;59(6):3197-207.
    PMID: 25801553 DOI: 10.1128/AAC.05013-14
    The pharmacokinetics of sublingual artemether (ArTiMist) was investigated in two open-label studies. In study 1, 16 healthy males were randomized to each of four single-dose treatments administered in random order: (i) 15.0 mg of sublingual artemether (5 × 3.0 actuations), (ii) 30.0 mg of sublingual artemether (10 × 3.0 mg), (iii) 30.0 mg of sublingual artemether (5 × 6.0 mg), and (iv) 30.0 mg of artemether in tablet form. In study 2, 16 healthy males were randomized to eight 30.0-mg doses of sublingual artemether given over 5 days as either 10 3.0-mg or 5 6.0-mg actuations. Frequent blood samples were drawn postdose. Plasma artemether and dihydroartemisinin levels were measured using liquid chromatography-mass spectrometry. Population compartmental pharmacokinetic models were developed. In study 1, sublingual artemether absorption was biphasic, with both rate constants being greater than that of the artemether tablets (1.46 and 1.66 versus 0.43/h, respectively). Relative to the tablets, sublingual artemether had greater bioavailability (≥1.24), with the greatest relative bioavailability occurring in the 30.0-mg dose groups (≥1.58). In study 2, there was evidence that the first absorption phase accounted for between 32% and 69% of the total dose and avoided first-pass (FP) metabolism, with an increase in FP metabolism occurring in later versus earlier doses but with no difference in bioavailability between the dose actuations. Sublingual artemether is more rapidly and completely absorbed than are equivalent doses of artemether tablets in healthy adults. Its disposition appears to be complex, with two absorption phases, the first representing pregastrointestinal absorption, as well as dose-dependent bioavailability and autoinduction of metabolism with multiple dosing.
    Matched MeSH terms: Antimalarials/administration & dosage*; Antimalarials/pharmacokinetics*
  2. Simultaneous determination of artesunic acid and dihydroartemisinin in blood plasma by high-performance liquid chromatography for application in clinical pharmacological studies
    Navaratnam V, Mordi MN, Mansor SM
    J Chromatogr B Biomed Sci Appl, 1997 Apr 25;692(1):157-62.
    PMID: 9187395
    A selective reproducible high-performance liquid chromatographic assay for the simultaneous quantitative determination of the antimalarial compound artesunic acid (ARS), dihydroartemisinin (DQHS) and artemisinin (QHS), as internal standard, is described. After extraction from plasma, ARS and DQHS were analysed using an Econosil C8 column and a mobile phase of acetonitrile-0.05 M acetic acid (42:58, v/v) adjusted to pH 5.0 and electrochemical detection in the reductive mode. The mean recovery of ARS and DQHS over a concentration range of 50-200 ng/ml was 75.5% and 93.5%, respectively. The within-day coefficients of variation were 4.2-7.4% for ARS and 2.6-4.9% for DQHS. The day-to-day coefficients of variation were 1.6-9.6% and 0.5-8.3%, respectively. The minimum detectable concentration for ARS and DQHS in plasma was 4.0 ng/ml for both compounds. The method was found to be suitable for use in clinical pharmacological studies.
    Matched MeSH terms: Antimalarials/blood*; Antimalarials/pharmacokinetics
  3. Susceptibility of Malaysian Plasmodium falciparum isolates to antimalarial drugs after cryopreservation and 12 months of continuous in vitro culture
    Ang HH, Chan KL, Mak JW
    Chemotherapy, 1997 Sep-Oct;43(5):311-5.
    PMID: 9309363 DOI: 10.1159/000239583
    Eleven Malaysian Plasmodium falciparum isolates were cultured in vitro and later subjected to antimalarial evaluations in 96-well microtiter plates. After cryopreservation, the IC50 (nM) for ST 195, ST 196, ST 197, ST 244 and ST 245 isolates were, respectively: 180.9, 198.7, 482.0, 580.0 and 690.1 for chloroquine; 3.4, 3.4, 9.2, 4.0 and 5.8 for mefloquine; 21.9, 10.5, 40.7, 40.1 and 48.7 for quinine; 136.7, 58.8, 116.4, 29.4 and 95.4 for cycloguanil, and 48.3, 57.5, 47.4, 61.5 and 37.8 for pyrimethamine. Before cryopreservation they were 172.5, 141.5, 453.2, 636.0 and 651.6 nM for chloroquine; 4.8, 2.6, 9.0, 6.9 and 5.8 nM for mefloquine; 21.3, 8.3, 41.9, 49.6 and 40.1 nM for quinine, 129.9, 47.3, 109.3, 30.6 and 95.4 nM for cycloguanil, and 45.4, 47.4, 40.2, 66.3 and 36.0 nM for pyrimethamine. IC50 (nM) for Gombak A, Gombak C, ST 9, ST 12, ST 85 and ST 148 isolates after 12 months of continuous in vitro culture were, respectively: 477.0, 492.3, 367.1, 809.4, 566.5 and 341.8 for chloroquine; 2.9, 11.1, 8.5, 16.9, 5.3 and 4.2 for mefloquine; 6.2, 58.3, 52.7, 36.7, 31.8 and 26.2 for quinine; 154.5, 57.2, 130.3, 94.2, 81.4 and 102.9 for cycloguanil, 26.9, 24.9, 43.8, 31.0, 14.1 and 56.7 for pyrimethamine. Before the 12-month culture they were 472.3, 452.9, 352.7, 773.7, 702.7 and 322.7 nM for chloroquine; 2.6, 13.2, 8.5, 17.2, 5.0 and 4.0 nM for mefloquine; 6.2, 85.4, 53.9, 38.5, 35.8 and 38.5 nM for quinine; 106.8, 74.3, 112.4, 89.8, 91.8 and 103.3 nM for cycloguanil, and 26.9, 31.4, 47.0, 28.1, 14.9 and 56.7 nM for pyrimethamine. Thus none of these isolates differed in their original susceptibilities after either of these procedures.
    Matched MeSH terms: Antimalarials/pharmacology*
  4. Correspondence: Misuse of fansidar
    O'Holohan DR, Dondero TJ, Ponnampalam JT
    Med J Malaysia, 1973 Jun;27(4):310.
    PMID: 4270792
    Matched MeSH terms: Antimalarials/administration & dosage*
  5. Land ownership and anti-malaria law in Malaya
    HUDSON JH
    J Trop Med Hyg, 1948 Feb;51(2):33-40.
    PMID: 18906095
    Matched MeSH terms: Antimalarials*
  6. Combination mode of antimalarial drug mefloquine and human serum albumin: Insights from spectroscopic and docking approaches
    Musa KA, Ridzwan NFW, Mohamad SB, Tayyab S
    Biopolymers, 2020 Feb;111(2):e23337.
    PMID: 31691964 DOI: 10.1002/bip.23337
    The interaction between mefloquine (MEF), the antimalarial drug, and human serum albumin (HSA), the main carrier protein in blood circulation, was explored using fluorescence, absorption, and circular dichroism spectroscopic techniques. Quenching of HSA fluorescence with MEF was characterized as static quenching and thus confirmed the complex formation between MEF and HSA. Association constant values for MEF-HSA interaction were found to fall within the range of 3.79-5.73 × 104  M-1 at various temperatures (288, 298, and 308 K), which revealed moderate binding affinity. Hydrogen bonds and hydrophobic interactions were predicted to connect MEF and HSA together in the MEF-HSA complex, as deduced from the thermodynamic data (ΔS = +133.52 J mol-1 K-1 and ΔH = +13.09 kJ mol-1 ) of the binding reaction and molecular docking analysis. Three-dimensional fluorescence spectral analysis pointed out alterations in the microenvironment around aromatic amino acid (tryptophan and tyrosine) residues of HSA consequent to the addition of MEF. Circular dichroic spectra of HSA in the wavelength ranges of 200-250 and 250-300 nm hinted smaller changes in the protein's secondary and tertiary structures, respectively, induced by MEF binding. Noncovalent conjugation of MEF to HSA bettered protein thermostability. Site marker competitive drug displacement results suggested HSA Sudlow's site I as the MEF binding site, which was also supported by molecular docking analysis.
    Matched MeSH terms: Antimalarials/chemistry*
  7. Fulltext Primaquine and chloroquine nano-sized solid dispersion-loaded dissolving microarray patches for the improved treatment of malaria caused by Plasmodium vivax
    Anjani QK, Volpe-Zanutto F, Hamid KA, Sabri AHB, Moreno-Castellano N, Gaitán XA, et al.
    J Control Release, 2023 Sep;361:385-401.
    PMID: 37562555 DOI: 10.1016/j.jconrel.2023.08.009
    Malaria is a global parasitic infection that leads to substantial illness and death. The most commonly-used drugs for treatment of malaria vivax are primaquine and chloroquine, but they have limitations, such as poor adherence due to frequent oral administration and gastrointestinal side effects. To overcome these limitations, we have developed nano-sized solid dispersion-based dissolving microarray patches (MAPs) for the intradermal delivery of these drugs. In vitro testing showed that these systems can deliver to skin and receiver compartment up to ≈60% of the payload for CQ-based dissolving MAPs and a total of ≈42% of drug loading for PQ-based dissolving MAPs. MAPs also displayed acceptable biocompatibility in cell tests. Pharmacokinetic studies in rats showed that dissolving MAPs could deliver sustained plasma levels of both PQ and CQ for over 7 days. Efficacy studies in a murine model for malaria showed that mice treated with PQ-MAPs and CQ-MAPs had reduced parasitaemia by up to 99.2%. This pharmaceutical approach may revolutionise malaria vivax treatment, especially in developing countries where the disease is endemic. The development of these dissolving MAPs may overcome issues associated with current pharmacotherapy and improve patient outcomes.
    Matched MeSH terms: Antimalarials*
  8. Synthesis and biological evaluation of hydantoin derivatives as potent antiplasmodial agents
    Chin EZ, Chang WJ, Tan HY, Liew SY, Lau YL, Ng YL, et al.
    Bioorg Med Chem Lett, 2024 May 01;103:129701.
    PMID: 38484804 DOI: 10.1016/j.bmcl.2024.129701
    Malaria, a devastating disease, has claimed numerous lives and caused considerable suffering, with young children and pregnant women being the most severely affected group. However, the emergence of multidrug-resistant strains of Plasmodium and the adverse side effects associated with existing antimalarial drugs underscore the urgent need for the development of novel, well-tolerated, and more efficient drugs to combat this global health threat. To address these challenges, six new hydantoins derivatives were synthesized and evaluated for their in vitro antiplasmodial activity. Notably, compound 2c exhibited excellent inhibitory activity against the tested Pf3D7 strain, with an IC50 value of 3.97 ± 0.01 nM, three-fold better than chloroquine. Following closely, compound 3b demonstrated an IC50 value of 27.52 ± 3.37 µM against the Pf3D7 strain in vitro. Additionally, all the hydantoins derivatives tested showed inactive against human MCR-5 cells, with an IC50 value exceeding 100 μM. In summary, the hydantoin derivative 2c emerges as a promising candidate for further exploration as an antiplasmodial compound.
    Matched MeSH terms: Antimalarials*
  9. Physico-chemical effects of the major quassinoids in a standardized Eurycoma longifolia extract (Fr 2) on the bioavailability and pharmacokinetic properties, and their implications for oral antimalarial activity
    Low BS, Teh CH, Yuen KH, Chan KL
    Nat Prod Commun, 2011 Mar;6(3):337-41.
    PMID: 21485270
    A simple validated LC-UV method for the phytochemical analysis of four bioactive quassinoids, 13alpha(21)-epoxyeurycomanone (EP), eurycomanone (EN), 13alpha,21-dihydroeurycomanone (ED) and eurycomanol (EL) in rat plasma following oral (200 mg/kg) and intravenous administration (10 mg/kg) of a standardized extract Fr 2 of Eurycoma longifolia Jack was developed for pharmacokinetic and bioavailability studies. The extract Fr 2 contained 4.0%, 18.5%, 0.7% and 9.5% of EP, EN, ED and EL, respectively. Following intravenous administration, EP displayed a relatively longer biological half-life (t1/2 = 0.75 +/- 0.25 h) due primarily to its lower elimination rate constant (k(e)) of 0.84 +/- 0.26 h(-1)) when compared with the t1/2 of 0.35 +/- 0.04 h and k(e) of 2.14 +/- 0.27 h(-1), respectively of EN. Following oral administration, EP showed a higher C(max) of 1.61 +/- 0.41 microg/mL over that of EN (C(max) = 0.53 +/- 0.10 microg/mL). The absolute bioavailability of EP was 9.5-fold higher than that of EN, not because of chemical degradation since both quassinoids were stable at the simulated gastric pH of 1. Instead, the higher log K(ow) value of EP (-0.43) contributed to greater membrane permeability over that of EN (log K(ow) = -1.46) at pH 1. In contrast, EL, being in higher concentration in the extract than EP, was not detected in the plasma after oral administration because of substantial degradation by the gastric juices after 2 h. Similarly, ED, being unstable at the acidic pH and together with its low concentration in Fr 2, was not detectable in the rat plasma. In conclusion, upon oral administration of the bioactive standardized extract Fr 2, EP and EN may be the only quassinoids contributing to the overall antimalarial activity; this is worthy of further investigation.
    Matched MeSH terms: Antimalarials/pharmacokinetics; Antimalarials/pharmacology*; Antimalarials/chemistry*
  10. Ethnobotanical study on some Malaysian anti-malarial plants: a community based survey
    Al-Adhroey AH, Nor ZM, Al-Mekhlafi HM, Mahmud R
    J Ethnopharmacol, 2010 Oct 28;132(1):362-4.
    PMID: 20723596 DOI: 10.1016/j.jep.2010.08.006
    Various plants species are used in the traditional medicine for the treatment of malaria. This is the first community based ethnobotanical study in Peninsular Malaysia.
    Matched MeSH terms: Antimalarials/isolation & purification; Antimalarials/pharmacology*; Antimalarials/therapeutic use
  11. Development of a capillary electrophoresis method for the enantioselective estimation of primaquine in pharmaceutical formulations
    Elbashir AA, Saad B, Ali AS, Saleh MI
    J AOAC Int, 2008 6 24;91(3):536-41.
    PMID: 18567298
    A capillary electrophoresis (CE) method has been developed that allows the separation and estimation of primaquine enantiomers using hydroxypropyl-gamma-cyclodextrin (HP-gamma -CD) as a chiral selector. The influence of chemical and instrumental parameters on the separation, such as type and concentration of CD, buffer concentration, buffer pH, applied voltage, capillary temperature, and injection time, were investigated. Good separation of the racemic mixture of primaquine was achieved using a fused-silica capillary (52.5 cm effective length x 50 microm id) and a background electrolyte composed of tris-phosphate buffer solution (50 mM, pH 2.5) containing 15 mM HP-gamma-CD as a chiral selector. The recommended applied voltage, capillary temperature, and injection time were 15 kV, 25 degrees C, and 6 s, respectively. Within-day and interday reproducibility of peak area and migration time gave relative standard deviation values ranging from 1.05-3.30%. Good recoveries (range of 96.8-104.9%) were obtained from the determination of placebos that were spiked with 0.25-1.00 mg/L primaquine. The proposed CE method was successfully applied to the assay of primaquine diphosphate in pharmaceutical formulations (tablets).
    Matched MeSH terms: Antimalarials/isolation & purification; Antimalarials/standards; Antimalarials/chemistry
  12. The Potential of β Carbolin Alkaloids to Hinder Growth and Reverse Chloroquine Resistance in Plasmodium falciparum
    Ibraheem ZO, Abdul Majid R, Mohd Noor S, Mohd Sidek H, Basir R
    Iran J Parasitol, 2015 Oct-Dec;10(4):577-83.
    PMID: 26811724
    Nowadays, scourge of malaria as a fatalistic disease has increased due to emergence of drug resistance and tolerance among different strains of Plasmodium falciparum. Emergence of chloroquine (CQ) resistance has worsened the calamity as CQ is still considered the most efficient, safe and cost effective drug among other antimalarials. This urged the scientists to search for other alternatives or sensitizers that may be able to augment CQ action and reverse its resistance.
    Matched MeSH terms: Antimalarials
  13. Notes on a clinical investigation of the treatment of malaria by atebrin musonat injections
    Vardy EC
    Malayan Medical Journal, 1935;10:67-77.
    Matched MeSH terms: Antimalarials
  14. Epileptiform fits following injection of atebrin-musonat
    Malayan Medical Journal, 1936;11:182.
    Matched MeSH terms: Antimalarials
  15. Toxic effects associated with the use of atebrin
    Green R
    Malayan Medical Journal, 1934;9:22-32.
    Matched MeSH terms: Antimalarials
  16. Fulltext Pharmacokinetics of a novel sublingual spray formulation of the antimalarial drug artemether in African children with malaria
    Salman S, Bendel D, Lee TC, Templeton D, Davis TM
    Antimicrob Agents Chemother, 2015;59(6):3208-15.
    PMID: 25801552 DOI: 10.1128/AAC.05014-14
    The pharmacokinetics of sublingual artemether (ArTiMist) was investigated in 91 young African children with severe malaria or who could not tolerate oral antimalarial therapy. Each received 3.0 mg/kg of body weight of artemether at 0, 8, 24, 36, 48, and 60 h or until the initiation of oral treatment. Few blood samples were drawn postdose. Plasma artemether and dihydroartemisinin (DHA) levels were measured using liquid chromatography-mass spectrometry, and the data were analyzed using established population compartmental pharmacokinetic models. Parasite clearance was prompt (median parasite clearance time, 24 h), and there were no serious adverse events. Consistent with studies in healthy adults (S. Salman, D. Bendel, T. C. Lee, D. Templeton, and T. M. E. Davis, Antimicrob Agents Chemother 59:3197-3207, 2015, http://dx.doi.org/10.1128/AAC.05013-14), the absorption of sublingual artemether was biphasic, and multiple dosing was associated with the autoinduction of the metabolism of artemether to DHA (which itself has potent antimalarial activity). In contrast to studies using healthy volunteers, pharmacokinetic modeling indicated that the first absorption phase did not avoid first-pass metabolism, suggesting that the drug is transferred to the upper intestine through postdose fluid/food intake. Simulations using the present data and those from an earlier study in older Melanesian children with uncomplicated malaria treated with artemether-lumefantrine tablets suggested that the bioavailability of sublingual artemether was at least equivalent to that after conventional oral artemether-lumefantrine (median [interquartile range] areas under the concentration-time curve for artemether, 3,403 [2,471 to 4,771] versus 3,063 [2,358 to 4,514] μg · h/liter, respectively; and for DHA, 2,958 [2,146 to 4,278] versus 2,839 [1,812 to 3,488] μg · h/liter, respectively; P ≥ 0.42). These findings suggest that sublingual artemether could be used as prereferral treatment for sick children before transfer for definitive management of severe or moderately severe malaria.
    Matched MeSH terms: Antimalarials/administration & dosage*; Antimalarials/pharmacokinetics*; Antimalarials/therapeutic use
  17. Fulltext Antiplasmodial properties of some Malaysian medicinal plants
    Noor Rain A, Khozirah S, Mohd Ridzuan MA, Ong BK, Rohaya C, Rosilawati M, et al.
    Trop Biomed, 2007 Jun;24(1):29-35.
    PMID: 17568375 MyJurnal
    Seven Malaysian medicinal plants were screened for their antiplasmodial activities in vitro. These plants were selected based on their traditional claims for treatment or to relieve fever. The plant extracts were obtained from Forest Research Institute Malaysia (FRIM). The antiplasmodial activities were carried out using the pLDH assay to Plasmodium falciparum D10 strain (sensitive strain) while the cytotoxic activities were carried out towards Madin- Darby bovine kidney (MDBK) cells using MTT assay. The concentration of extracts used for both screening assays were from the highest concentration 64 microg/ml, two fold dilution to the lowest concentration 0.03 microg/ml. Goniothalamus macrophyllus (stem extract) showed more than 60% growth inhibition while Goniothalamus scortechinii root and stem extract showed a 90% and more than 80% growth inhibition at the last concentration tested, 0.03 microg/ml. The G. scortechini (leaves extract) showed an IC50 (50% growth inhibition) at 8.53 microg/ml, Ardisia crispa (leaves extract) demonstrated an IC50 at 5.90 +/- 0.14 microg/ml while Croton argyratus (leaves extract) showed a percentage inhibition of more than 60% at the tested concentration. Blumea balsamifera root and stem showed an IC50 at 26.25 +/- 2.47 microg/ml and 7.75 +/- 0.35 microg/ ml respectively. Agathis borneensis (leaves extract) demonstrated a 50% growth inhibition at 11.00 +/- 1.41 microg/ml. The study gives preliminary scientific evidence of these plant extracts in line with their traditional claims.
    Matched MeSH terms: Antimalarials/adverse effects; Antimalarials/pharmacology*; Antimalarials/chemistry
  18. Single dose pharmacokinetics of oral artemether in healthy Malaysian volunteers
    Mordi MN, Mansor SM, Navaratnam V, Wernsdorfer WH
    Br J Clin Pharmacol, 1997 Apr;43(4):363-5.
    PMID: 9146847
    AIMS: To determine the pharmacokinetics of artemether (ARM) and its principal active metabolite, dihydroartemisinin (DHA) in healthy volunteers.

    METHODS: Six healthy male Malaysian subjects were given a single oral dose of 200 mg artemether. Blood samples were collected to 72 h. Plasma concentrations of the two compounds were measured simultaneously by reversed-phase h.p.l.c. with electro-chemical detection in the reductive mode.

    RESULTS: Mean (+/- s.d.) maximum concentrations of ARM, 310 +/- 153 micrograms l-1, were reached 1.88 +/- 0.21 h after drug intake. The mean elimination half-life was 2.00 +/- 0.59 h, and the mean AUC 671 +/- 271 micrograms l-1 h. The mean Cmax of DHA, 273 +/- 64 micrograms l-1 was observed at 1.92 +/- 0.13 h. The mean AUC of DHA was 753 +/- 233 micrograms h l-1'. ARM and DHA were stable at < or = -20 degrees C for at least 4 months in plasma samples.

    CONCLUSIONS: The relatively short half-life of ARM may be one of the factors responsible for the poor radical cure rate of falciparum malaria with regimens employing daily dosing. In view of the rapid loss of DHA in plasma samples held at room temperature (26 degrees C) it is recommended to store them at a temperature of < or = -20 degrees C as early as possible after sample collection.

    Matched MeSH terms: Antimalarials/administration & dosage; Antimalarials/blood; Antimalarials/pharmacokinetics*
  19. Epileptiform fits in a case of malaria treated with injections of atebrin
    Menon PK
    Malayan Medical Journal, 1936;11:121.
    Matched MeSH terms: Antimalarials
  20. Fulltext Plasmodium knowlesi malaria in Malaysia
    Singh B, Daneshvar C
    Med J Malaysia, 2010 Sep;65(3):166-72.
    PMID: 21939162 MyJurnal
    Plasmodium knowlesi, a simian malaria parasite, is now recognised as the fifth cause of human malaria and can lead to fatal infections in humans. Knowlesi malaria cases are widely distributed in East and West Malaysia and account for more than 50% of admissions for malaria in certain hospitals in the state of Sarawak. This paper will begin with a description of the early studies on P. knowlesi, followed by a review of the epidemiology, diagnosis, clinical and laboratory features, and treatment of knowlesi malaria.
    Matched MeSH terms: Antimalarials/therapeutic use
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