Displaying publications 21 - 40 of 86 in total

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  1. Fulltext Differential responses of Vibrio sp. to young and mature leaves extracts of Terminalia catappa L
    Nadirah, M., Wee, T. L., Najiah, M.
    International Food Research Journal, 2013;20(2):961-966.
    MyJurnal
    Young and mature leaves of Terminalia catappa of alcoholic and aqueous extracts were evaluated for in vitro antibacterial activity against Vibrio sp. isolated from aquatic animals. Young leaves of T. catappa showed higher antibacterial activity when compared to mature leaves against Vibrio parahemolyticus, with methanolic and aqueous extracts exhibited the largest inhibition zones, 23 and 24 mm, respectively as determined by disc diffusion technique. Ethanolic extract of young leaves showed the lowest MIC and MBC at 3.13 mg/ml and 6.25 mg/ml, respectively. Both alcoholic and aqueous extracts of young and matures leaves exhibit variations in protein, RNA as well as pyrine and pyrimidines leakage of Vibrio sp. Cell membrane disruption is proposed as the mechanism of action of T. catappa leaves extract against Vibrio sp.
    Matched MeSH terms: Pyrimidines
  2. Method development and validation for the simultaneous determination of imatinib mesylate and N-desmethyl imatinib using rapid resolution high performance liquid chromatography coupled with UV-detection
    Tan KL, Ankathil R, Gan SH
    J Chromatogr B Analyt Technol Biomed Life Sci, 2011 Nov 15;879(30):3583-91.
    PMID: 22000961 DOI: 10.1016/j.jchromb.2011.09.048
    We developed a simple and sensitive method for the simultaneous detection of imatinib mesylate (IM) and its active metabolite, N-desmethyl imatinib (M1), in human serum samples. Separation was successfully achieved using an Agilent(®) ZORBAX Eclipse plus C(18) reversed phase column (50 mm × 2.1 mm, i.d.; 1.8 μm) under isocratic mobile phase conditions consisting of acetonitrile: 0.02 M potassium dihydrogen phosphate with 0.2% triethylamine at pH 3 (25:75, v/v) and ultra-violet detection was achieved at 235 nm. Extraction of the target compounds was completed using 100% cold acetonitrile. Good linearities (r(2)>0.99) for both IM and M1 were achieved for the concentration ranges of 50-1800 ng/mL and 50-360 ng/mL, respectively. The detection limits were 20 ng/mL and 10 ng/mL for M1 and IM, respectively. The intra- and inter-day precisions were less than 1% with percent recoveries of more than 90%. The method was successfully applied to calculate the pharmacokinetic parameters of chronic myeloid leukemia patients receiving imatinib. The method is suitable to be routinely applied for determination of IM and M1 in serum.
    Matched MeSH terms: Pyrimidines/blood*; Pyrimidines/metabolism; Pyrimidines/chemistry
  3. Synthesis, antibacterial activity and cytotoxicity of new fused pyrazolo[1,5-a]pyrimidine and pyrazolo[5,1-c][1,2,4]triazine derivatives from new 5-aminopyrazoles
    Al-Adiwish WM, Tahir MI, Siti-Noor-Adnalizawati A, Hashim SF, Ibrahim N, Yaacob WA
    Eur J Med Chem, 2013 Jun;64:464-76.
    PMID: 23669354 DOI: 10.1016/j.ejmech.2013.04.029
    New 5-aminopyrazoles 2a-c were prepared in high yields from the reaction of known α,α-dicyanoketene-N,S-acetals 1a-c with hydrazine hydrate under reflux in ethanol. These compounds were utilized as intermediates to synthesize pyrazolo[1,5-a]-pyrimidines 3a-c, 4a-d, 5a-c, and 6a-c, as well as pyrazolo[5,1-c][1,2,4]triazines 7a-c and 8a-c, by the reaction of 2-[bis(methylthio)methylene]malononitrile, α,α-dicyanoketene-N,S-acetals 1a-b, acetylacetone, acetoacetanilide as well as acetylacetone, and malononitrile, respectively. Furthermore, cyclization of 2a-c with pentan-2,5-dione yielded the corresponding 5-pyrrolylpyrazoles 9a-c. Moreover, fusion of 2a-c with acetic anhydride resulted in the corresponding 1-acetyl-1H-pyrazoles 10a-c. The antibacterial activity and cytotoxicity against Vero cells of several selected compounds are also reported.
    Matched MeSH terms: Pyrimidines/chemical synthesis; Pyrimidines/pharmacology*; Pyrimidines/chemistry
  4. Disposition and tissue distribution of imatinib in a liposome formulation after intravenous bolus dose to mice
    Moo KS, Radhakrishnan S, Teoh M, Narayanan P, Bukhari NI, Segarra I
    Yao Xue Xue Bao, 2010 Jul;45(7):901-8.
    PMID: 20931790
    Imatinib is an efficacious anticancer drug with a spectrum of potential antitumour applications limited by poor biodistribution at therapeutic concentrations to the tissues of interest. We assess the pharmacokinetic and tissue distribution profile of imatinib in a liposome formulation. Its single dose (6.25 mg x kg(-1)) in a liposome formulation was administered iv to male mice. Imatinib concentration was measured in plasma, spleen, liver, kidney and brain using a HPLC assay. Non-compartmental pharmacokinetic approach was used to assess the disposition parameters. The plasma disposition profile was biphasic with a plateau-like second phase. The AUC(0-->infinity) was 11.24 microg x h x mL(-1), the elimination rate constant (k(el)) was 0.348 h(-1) and the elimination half life (t(1/2)) was 2.0 h. The mean residence time (MRT) was 2.59 h, V(SS) was 1.44 L x kg(-1) and clearance was 0.56 L x h x kg(-1). Liver achieved the highest tissue exposure: CMAX = 18.72 microg x mL(-1); AUC(0-->infinity)= 58.18 microg x h x mL(-1) and longest t(1/2) (4.29 h) and MRT (5.31 h). Kidney and spleen AUC(0-->infinity) were 47.98 microg x h x mL(-1) and 23.46 microg x h x mL(-1), respectively. Half-life was 1.83 h for the kidney and 3.37 h for the spleen. Imatinib penetrated into the brain reaching approximately 1 microg x g(-1). Upon correction by organ blood flow the spleen showed the largest uptake efficiency. Liposomal imatinib presented extensive biodistribution. The drug uptake kinetics showed mechanism differences amongst the tissues. These findings encourage the development of novel imatinib formulations to treat other cancers.
    Matched MeSH terms: Pyrimidines/administration & dosage; Pyrimidines/blood; Pyrimidines/pharmacokinetics*
  5. Crystallographic, vibrational and DFT studies of 1-(2-hydroxy-4,5-dimethylphenyl)ethanone
    Chidan Kumar CS, Parlak C, Fun HK, Tursun M, Bilge M, Chandraju S, et al.
    Spectrochim Acta A Mol Biomol Spectrosc, 2015 Oct 5;149:762-70.
    PMID: 25989614 DOI: 10.1016/j.saa.2015.05.012
    Molecular structure and properties of 1-(2-hydroxy-4,5-dimethylphenyl)ethanone were experimentally investigated by X-ray diffraction technique and vibrational spectroscopy. Experimental results on the molecular structure of the reported compound were supported with computational studies using the density functional theory (DFT), with the Becke-3-Lee-Yang-Parr (B3LYP) functional and the 6-311+G(3df,p) basis set. Potential energy distribution (PED) and potential energy surface (PES) analyses were performed to identify characteristic frequencies and reliable conformational analysis correspondingly. The compound crystallizes in monoclinic space group C2/c with the CO up-OH down conformation. There is a good agreement between the experimentally determined geometrical parameters and vibrational frequencies of the compound to those predicted theoretically.
    Matched MeSH terms: Pyrimidines
  6. Synthesis, NMR, FT-IR, X-ray structural characterization, DFT analysis and isomerism aspects of 5-(2,6-dichlorobenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione
    Barakat A, Al-Najjar HJ, Al-Majid AM, Soliman SM, Mabkhot YN, Shaik MR, et al.
    Spectrochim Acta A Mol Biomol Spectrosc, 2015 Aug 5;147:107-16.
    PMID: 25827772 DOI: 10.1016/j.saa.2015.03.016
    The synthesis and spectral characterization of the 5-(2,6-dichlorobenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione;3 was reported. The solid state molecular structure of 3 was studied using X-ray crystallography. The relative stabilities of the seven possible isomers of 3 were calculated by DFT/B3LYP method using 6-311 G(d,p) basis set. The calculated total energies and thermodynamic parameters were used to predict the relative stabilities of these isomers. The effect of solvent polarity on the relative stability of these isomers was studied at the same level of theory using PCM. It was found that the keto form, (T0), is the most stable isomer both in the gaseous state and solution. In solution, the calculated total energies of all isomers are decreased indicating that all isomers are stabilized by the solvent effect. The vibrational spectra of the most stable isomer, 3(T0) are calculated using the same level of theory and the results are compared with the experimentally measured FTIR spectra. Good correlation was obtained between the experimental and calculated vibrational frequencies (R(2)=0.9992). The electronic spectra of 3(T0) in gas phase as well as in solutions were calculated using the TD-DFT method. All the predicted electronic transitions showed very little spectral shifts and increase in the intensity of absorption due to solvent effect. Also the (1)H- and (13)C-NMR chemical shifts of the stable isomer were calculated and the results were correlated with the experimental data. Good correlations between the experimental and calculated chemical shifts were obtained.
    Matched MeSH terms: Pyrimidines
  7. Synthesis, in vitro biological activities and in silico study of dihydropyrimidines derivatives
    Barakat A, Islam MS, Al-Majid AM, Ghabbour HA, Fun HK, Javed K, et al.
    Bioorg Med Chem, 2015 Oct 15;23(20):6740-8.
    PMID: 26381063 DOI: 10.1016/j.bmc.2015.09.001
    We describe here the synthesis of dihydropyrimidines derivatives 3a-p, and evaluation of their α-glucosidase enzyme inhibition activities. Compounds 3b (IC50=62.4±1.5 μM), 3c (IC50=25.3±1.26 μM), 3d (IC50=12.4±0.15 μM), 3e (IC50=22.9±0.25 μM), 3g (IC50=23.8±0.17 μM), 3h (IC50=163.3±5.1 μM), 3i (IC50=30.6±0.6 μM), 3m (IC50=26.4±0.34 μM), and 3o (IC50=136.1±6.63 μM) were found to be potent α-glucosidase inhibitors in comparison to the standard drug acarbose (IC50=840±1.73 μM). The compounds were also evaluated for their in vitro cytotoxic activity against PC-3, HeLa, and MCF-3 cancer cell lines, and 3T3 mouse fibroblast cell line. All compounds were found to be non cytotoxic, except compounds 3f and 3m (IC50=17.79±0.66-20.44±0.30 μM), which showed a weak cytotoxic activity against the HeLa, and 3T3 cell lines. In molecular docking simulation study, all the compounds were docked into the active site of the predicted homology model of α-glucosidase enzyme. From the docking result, it was observed that most of the synthesized compounds showed interaction through carbonyl oxygen atom and polar phenyl ring with active site residues of the enzyme.
    Matched MeSH terms: Pyrimidines/chemical synthesis; Pyrimidines/pharmacology*; Pyrimidines/chemistry
  8. Fulltext Synthesis of 2,4-Diaminopyrimidine Core-Based Derivatives and Biological Evaluation of Their Anti-Tubercular Activities
    Ouyang Y, Yang H, Zhang P, Wang Y, Kaur S, Zhu X, et al.
    Molecules, 2017 Sep 22;22(10).
    PMID: 28937657 DOI: 10.3390/molecules22101592
    Tuberculosis (TB) is a chronic, potentially fatal disease caused by Mycobacterium tuberculosis (Mtb). The dihyrofolate reductase in Mtb (mt-DHFR) is believed to be an important drug target in anti-TB drug development. This enzyme contains a glycerol (GOL) binding site, which is assumed to be a useful site to improve the selectivity towards human dihyrofolate reductase (h-DHFR). There have been previous attempts to design drugs targeting the GOL binding site, but the designed compounds contain a hydrophilic group, which may prevent the compounds from crossing the cell wall of Mtb to function at the whole cell level. In the current study, we designed and synthesized a series of mt-DHFR inhibitors that contain a 2,4-diaminopyrimidine core with side chains to occupy the glycerol binding site with proper hydrophilicity for cell entry, and tested their anti-tubercular activity against Mtb H37Ra. Among them, compound 16l showed a good anti-TB activity (MIC = 6.25 μg/mL) with a significant selectivity against vero cells. In the molecular simulations performed to understand the binding poses of the compounds, it was noticed that only side chains of a certain size can occupy the glycerol binding site. In summary, the novel synthesized compounds with appropriate side chains, hydrophobicity and selectivity could be important lead compounds for future optimization towards the development of future anti-TB drugs that can be used as monotherapy or in combination with other anti-TB drugs or antibiotics. These compounds can also provide much information for further studies on mt-DHFR. However, the enzyme target of the compounds still needs to be confirmed by pure mt-DHFR binding assays.
    Matched MeSH terms: Pyrimidines/chemistry*
  9. Development of solid dispersion systems of dapivirine to enhance its solubility
    Gorajana A, Ying CC, Shuang Y, Fong P, Tan Z, Gupta J, et al.
    Curr Drug Deliv, 2013 Jun;10(3):309-16.
    PMID: 23360246
    Dapivirine, formerly known as TMC 120, is a poorly-water soluble anti-HIV drug, currently being developed as a vaginal microbicide. The clinical use of this drug has been limited due to its poor solubility. The aim of this study was to design solid dispersion systems of Dapivirine to improve its solubility. Solid dispersions were prepared by solvent and fusion methods. Dapivirine release from the solid dispersion system was determined by conducting in-vitro dissolution studies. The physicochemical characteristics of the drug and its formulation were studied using Differential Scanning Calorimetry (DSC), powder X-ray Diffraction (XRD), Fourier-transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM). A significant improvement in drug dissolution rate was observed with the solid dispersion systems. XRD, SEM and DSC results indicated the transformation of pure Dapivirine which exists in crystalline form into an amorphous form in selected solid dispersion formulations. FTIR and HPLC analysis confirmed the absence of drug-excipient interactions. Solid dispersion systems can be used to improve the dissolution rate of Dapivirine. This improvement could be attributed to the reduction or absence of drug crystallinity, existence of drug particles in an amorphous form and improved wettability of the drug.
    Matched MeSH terms: Pyrimidines/chemistry*
  10. Fulltext In vitro activity of fluconazole and voriconazole against clinical isolates of Candida spp. by E-test method
    Madhavan P, Jamal F, Chong PP, Ng KP
    Trop Biomed, 2010 Aug;27(2):200-7.
    PMID: 20962716 MyJurnal
    The in vitro susceptibility of clinical Candida isolates towards fluconazole and voriconazole was determined using the E-test method. A total of 41 clinical isolates recovered from patients since 2004 until 2009 from two local hospitals in Kuala Lumpur, Malaysia were used. These comprised Candida tropicalis, Candida albicans, Candida krusei, Candida parapsilosis, Candida rugosa, Candida dubliniensis and Candida glabrata. Strains from American Type Culture Collection were used as quality control. Lawn cultures of the isolates on RPMI-1640 agar medium supplemented with 2% glucose were incubated with the E-test strips at 35ºC for 48 h. Our results show that 71% were susceptible to fluconazole and 90% were susceptible to voriconazole. All strains of C. krusei were resistant to fluconazole and 50% were susceptible in a dose-dependent manner to voriconazole. There were 66% and 33% of C. glabrata that were resistant to fluconazole and voriconazole. Our study revealed that majority of the clinical Candida isolates was susceptible to fluconazole and voriconazole with a small percentage being resistant to both the drugs.
    Matched MeSH terms: Pyrimidines/pharmacology*
  11. Criofolinine and vernavosine, new pentacyclic indole alkaloids incorporating pyrroloazepine and pyridopyrimidine moieties derived from a common yohimbine precursor
    Nge CE, Gan CY, Lim KH, Ting KN, Low YY, Kam TS
    Org. Lett., 2014 Dec 19;16(24):6330-3.
    PMID: 25454201 DOI: 10.1021/ol503072g
    Two new indole alkaloids characterized by previously unencountered natural product skeletons, viz., criofolinine (1), incorporating a pyrroloazepine motif within a pentacyclic ring system, and vernavosine (2, isolated as its ethyl ether derivative 3, which on hydrolysis regenerated the putative precursor alkaloid 2), incorporating a pyridopyrimidine moiety embedded within a pentacyclic carbon framework, were isolated from a Malayan Tabernaemontana species. The structures and absolute configuration of these alkaloids were determined on the basis of NMR and MS analysis and confirmed by X-ray diffraction analysis.
    Matched MeSH terms: Pyrimidines/chemistry*
  12. Rapid determination of sildenafil and its analogues in dietary supplements using gas chromatography-triple quadrupole mass spectrometry
    Mokhtar SU, Chin ST, Kee CL, Low MY, Drummer OH, Marriott PJ
    J Pharm Biomed Anal, 2016 Mar 20;121:188-196.
    PMID: 26808068 DOI: 10.1016/j.jpba.2016.01.034
    Application of gas chromatography-triple quadrupole mass spectrometry for identification, confirmation and quantification of 6 phosphodiesterase-5 (PDE-5) inhibitors (sildenafil, dimethylsildenafil, homosildenafil, thiosildenafil, thiodimethylsildenafil and thiohomosildenafil) in dietary supplements was investigated. The MS was operated in multiple reaction monitoring mode, for better sensitivity and selectivity. In this manner, the method is adequate to reduce background noise with less interference from co-eluting compounds in the samples. Two different ionisation techniques, electron ionisation (EI) and chemical ionisation (CI), were studied and compared. The chromatographic separation was performed on a short 10 m non-polar capillary column without any derivatisation step. This permitted fast analysis for all analogues with retention time less than 11 min, for both techniques. Use of backflushing can aid method retention time reduction and improves column maintenance. Evaluation of method validation included limit of detection (LOD), lower limit of quantitation (LLOQ), linearity, precision and recovery were performed for both EI and CI techniques. The LOD obtained varied from 0.03 to 1.50 μg/g and the LLOQ ranged from 0.10 to 5.00 μg/g. Good calibration linearity was obtained for all analogues for both techniques, with correlation coefficients (r(2)) higher than 0.99. Mean recoveries of all analogues using CI show higher values (83.4-108.8%) than that of EI (61.9-91.1%). The intra- and inter-assay precisions were evaluated for all analogues at spiked concentration of 10 μg/g and the relative standard deviation was less than 15% for both methods. These methods were then successfully applied to dietary supplement samples without prior derivatisation, confirming that the samples were adulterated with sildenafil and/or its analogues.
    Matched MeSH terms: Pyrimidines/chemistry
  13. Fulltext Inequality in Drug Utilization among Chronic Myeloid Leukaemia Patients in Malaysia: A Cost-Utility Analysis
    Wan Puteh SE, Mohamad Selamat E, Aizuddin AN, Tumian NR, Sathar J
    Asian Pac J Cancer Prev, 2022 Dec 01;23(12):4253-4260.
    PMID: 36580008 DOI: 10.31557/APJCP.2022.23.12.4253
    BACKGROUND: The burden of chronic myeloid leukaemia (CML) is increasing due to longer patient survival, better life expectancy of the general population, and increasing drug prices. Funding is one of the main concerns in the choice of CML medication used worldwide; thus, patient assistance programmes were introduced to ensure accessibility to affordable treatment. In this study, we evaluated CML drug distribution inequality in Malaysia through patient assistance programmes, using pharmaco-economics methods to evaluate CML treatment from the care provider's perspective.

    METHODS: Patients with CML were recruited from outpatient haematological clinics at the national centre of intervention and referral for haematological conditions and a public teaching hospital. The health-related quality of life or utility scores were derived using the EuroQol EQ-5D-5L questionnaire. Costing data were obtained from the Ministry of Health Malaysia Casemix MalaysianDRG. Imatinib and nilotinib drug costs were obtained from the administration of the participating hospitals and pharmaceutical company.

    RESULTS: Of the 221 respondents in this study, 68.8% were imatinib users. The total care provider cost for CML treatment was USD23,014.40 for imatinib and USD43,442.69 for nilotinib. The governmental financial assistance programme reduced the total care provider cost to USD13,693.51 for imatinib and USD19,193.45 for nilotinib. The quality-adjusted life years (QALYs) were 17.87 and 20.91 per imatinib and nilotinib user, respectively. Nilotinib had a higher drug cost than imatinib, yet its users had better life expectancy, utility score, and QALYs. Imatinib yielded the lowest cost per QALYs at USD766.29.

    CONCLUSION: Overall, imatinib is more cost-effective than nilotinib for treating CML in Malaysia from the care provider's perspective. The findings demonstrate the importance of cancer drug funding assistance for ensuring that the appropriate treatments are accessible and affordable and that patients with cancer use and benefit from such patient assistance programmes. To establish effective health expenditure, drug distribution inequality should be addressed.

    Matched MeSH terms: Pyrimidines/adverse effects
  14. Fulltext A comparison of neoadjuvant therapies for gastroesophageal and gastric cancer on tumour resection rate: A network meta-analysis
    Herng SC, Htet NH, Naing C
    PLoS One, 2022;17(9):e0275186.
    PMID: 36156598 DOI: 10.1371/journal.pone.0275186
    BACKGROUND: Gastric cancer is one of the most common malignancies around the world, and a variety of neoadjuvant chemotherapies with different drug combinations are available for the treatment. R0 resection refers to a microscopically negative margin on resection, where no gross or microscopic tumour remains in the primary tumour. We aimed to find evidence on the relative effectiveness of neoadjuvant therapies for patients with advanced gastroesophageal and gastric cancer on the R0 resection rate.

    METHODS: Relevant randomised controlled trials were searched using appropriate keywords in health-related databases. We performed network meta-analysis within a frequentist framework. The endpoint assessed was the R0 resection rate. We assessed consistency and transitivity assumptions that are necessary for network meta-analysis. This study only used data from published studies. The need for consent from participants was waived by the Ethics Review Committee of the International Medical University in Malaysia.

    RESULTS: Six randomised controlled trials involving 1700 patients were identified. A network plot was formed with five neoadjuvant regimens [DLX (pyrimidine analogue + platinum compounds + chemoradiotherapy), DELX (pyrimidine analogue + epipodophylllotoxins/etoposide + platinum compounds + chemoradiotherapy), ADL (anthracycline + pyrimidine analogue + platinum compounds), ADM (anthracycline+ pyrimidine analogue + anti-folate compounds) and LTX (platinum compounds + taxane + chemoradiotherapy)] and surgery alone for management of patients with advanced gastroesophageal and gastric cancer. Assumptions required for a network meta-analysis such as consistency ((global test: Chi2 (1): 3.71; p:0.054)), and the transitivity in accord to the characteristics of interventions considered in this review were not violated. In the network comparison, surgery alone has a lower R0 resection rate compared with LTX (OR 0.2, 95%CI:0.01, 0.38) or DLX (OR 0.48, 95%CI: 0.29, 0.79). LTX has higher resection rate compared with DLX (OR 2.47, 95%CI: 1.08 to 5.63), DELX (OR 106.0, 95%CI: 25.29 to 444.21), ADM (OR 5.41, 95%CI: 1.56 to 18.78) or ADL (OR 3.12, 95%CI: 1.27 to 7.67). There were wide or very wide CIs in many of these comparisons. Overall certainty of the evidence was low or very low. Further research in this field is very likely to have an important impact on our confidence in the R0 resection rates between LTX versus other neoadjuvant chemotherapy is likely to change the estimate.

    CONCLUSIONS: Findings suggest that overall quality of evidence on the relative effectiveness of neoadjuvant chemotherapies was low to very low level. Therefore, we are very uncertain about the true effect of neoadjuvant therapies in the R0 resection rate in patients with gastroesophageal and gastric cancer. Future well-designed large trials are needed. To recruit large samples in this field, multicountry trials are recommended. Future trials also need to assess treatment-related adverse events, and patients-centered outcomes such as health-related quality of life.

    Matched MeSH terms: Pyrimidines/therapeutic use
  15. Metronidazole leads to enhanced uptake of imatinib in brain, liver and kidney without affecting its plasma pharmacokinetics in mice
    Tan SY, Kan E, Lim WY, Chay G, Law JH, Soo GW, et al.
    J Pharm Pharmacol, 2011 Jul;63(7):918-25.
    PMID: 21635257 DOI: 10.1111/j.2042-7158.2011.01296.x
    The pharmacokinetic interaction between metronidazole, an antibiotic-antiparasitic drug used to treat anaerobic bacterial and protozoal infections, and imatinib, a CYP3A4, P-glycoprotein substrate kinase inhibitor anticancer drug, was evaluated.
    Matched MeSH terms: Pyrimidines/adverse effects; Pyrimidines/blood; Pyrimidines/metabolism; Pyrimidines/pharmacokinetics*
  16. Fulltext Nilotinib dose-optimization in newly diagnosed chronic myeloid leukaemia in chronic phase: final results from ENESTxtnd
    Hughes TP, Munhoz E, Aurelio Salvino M, Ong TC, Elhaddad A, Shortt J, et al.
    Br J Haematol, 2017 10;179(2):219-228.
    PMID: 28699641 DOI: 10.1111/bjh.14829
    The Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Extending Molecular Responses (ENESTxtnd) study was conducted to evaluate the kinetics of molecular response to nilotinib in patients with newly diagnosed chronic myeloid leukaemia in chronic phase and the impact of novel dose-optimization strategies on patient outcomes. The ENESTxtnd protocol allowed nilotinib dose escalation (from 300 to 400 mg twice daily) in the case of suboptimal response or treatment failure as well as dose re-escalation for patients with nilotinib dose reductions due to adverse events. Among 421 patients enrolled in ENESTxtnd, 70·8% (95% confidence interval, 66·2-75·1%) achieved major molecular response (BCR-ABL1 ≤ 0·1% on the International Scale) by 12 months (primary endpoint). By 24 months, 81·0% of patients achieved major molecular response, including 63·6% (56 of 88) of those with dose escalations for lack of efficacy and 74·3% (55 of 74) of those with dose reductions due to adverse events (including 43 of 54 patients with successful re-escalation). The safety profile of nilotinib was consistent with prior studies. The most common non-haematological adverse events were headache, rash, and nausea; cardiovascular events were reported in 4·5% of patients (grade 3/4, 3·1%). The study was registered at clinicaltrials.gov (NCT01254188).
    Matched MeSH terms: Pyrimidines/administration & dosage*; Pyrimidines/adverse effects
  17. Fulltext Imatinib mesylate in the treatment of chronic myeloid leukemia: a local experience
    Bee PC, Gan GG, Teh A, Haris AR
    Med J Malaysia, 2006 Dec;61(5):547-52.
    PMID: 17623954 MyJurnal
    This study was done to assess the overall response rate of imatinib mesylate in local patients with chronic myeloid leukaemia. A total of 69 patients were recruited with male/female ratio of 7:3. Of the 69 patients; 35% were in the chronic phase, 41% were in the accelerated phase, 17% were in blast crisis and the remaining 7% were after stem cell transplantation. Complete haematological response rates of patients in chronic phase, accelerated phase and blast crisis were 95.8%, 96.4% and 41.7% respectively. Thirty-eight percent of patients achieved complete cytogenetic response and 10% achieved partial cytogenetic response. The cytogenetic response rates were 80%, 41.7% and 18.2% in chronic, accelerated and blast crisis phase respectively (p < 0.005). Twenty-six percent of patients developed anaemia, 13% had neutropenia and 12% had thrombocytopenia after starting on treatment. In addition, 14% of patients developed peripheral oedema, 13% complained of musculoskeletal pain, 12% had gastrointestinal side effects which include nausea, vomiting and diarrhoea, 9% had grade 1 hepatotoxicity, 7% developed skin rashes and one patient had an abnormal renal function test. Patients taking 600mg or higher dosage of imatinib had more gastrointestinal side effects. Patients who weighed less than 60kg had a much higher risk of developing anaemia. Anaemia was a negative predictor of cytogenetic response. Presenting high white blood cell counts and absence of cytogenetic response were also negative predictors of survival. Overall survival was 87%. This was affected by the different phases of disease (chronic phase was better than accelerated and blast crisis) (p < 0.001). In conclusion, our local CML patients did well on treatment with imatinib.
    Matched MeSH terms: Pyrimidines/adverse effects; Pyrimidines/therapeutic use*
  18. Late-onset marrow aplasia due to imatinib in newly diagnosed chronic phase chronic myeloid leukaemia
    Chng WJ, Tan LH
    Leuk. Res., 2005 Jun;29(6):719-20.
    PMID: 15863215
    Matched MeSH terms: Pyrimidines/adverse effects*; Pyrimidines/therapeutic use*
  19. Recurrent Trichosporon asahii glossitis: a case report
    Shareef BT, Harun A, Roziawati Y, Bahari IS, Deris ZZ, Ravichandran M
    J Contemp Dent Pract, 2008;9(3):114-20.
    PMID: 18335127
    This case report aims at describing an infection of the tongue as a manifestation of a Trichosporon asahii infection, its association with bronchial asthma and steroid administration, and to present a review of the literature pertaining to its antifungal susceptibility profile.
    Matched MeSH terms: Pyrimidines/administration & dosage; Pyrimidines/therapeutic use
  20. Understanding and Challenges in Taking Tyrosine Kinase Inhibitors among Malaysian Chronic Myeloid Leukemia Patients: A Qualitative Study
    Lim YM, Eng WL, Chan HK
    Asian Pac J Cancer Prev, 2017 07 27;18(7):1925-1930.
    PMID: 28749622
    Background: In Malaysia, the treatment for chronic myeloid leukemia (CML) has long been delivered under the
    Malaysian Patient Assistance Program (MYPAP), but research on identifying factors contributing to non-adherence to
    tyrosine kinase inhibitors (TKIs) is still limited. The current study explored understanding and challenges of Malaysian
    CML patients in taking imatinib and nilotinib. Methods: Semi-structured, face-to-face interviews were conducted
    with 13 CML patients receiving treatment at a public tertiary care center, and were analyzed using the content analysis
    approach. Results: The patients generally demonstrated inadequate knowledge, particularly of the natural history and
    staging of CML, the function of TKIs, and the methods used for monitoring the effectiveness of treatment. A number of
    them also had experiences of withholding, skipping or altering the treatment, mainly due to the life-disturbing adverse
    drug effects (ADRs), forgetfulness, and religious and social issues. Besides, most of them were found having limited
    skills in managing the ADRs, and not using prompts as reminders to take the medications. Furthermore, even though
    nilotinib was generally perceived as better tolerated as compared with imatinib, the inconvenience caused by the need
    to take it twice daily and on an empty stomach was constantly highlighted by the patients. Conclusion: While TKIs
    are widely used for CML treatment in Malaysia, the findings have revealed a lack of patient education and awareness,
    which warrants an integrated plan to reinforce medication adherence.
    Matched MeSH terms: Pyrimidines
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