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  1. Rasool AH, Rehman A, Wan Yusuf WN, Rahman AR
    Int J Clin Pharmacol Ther, 2003 Dec;41(12):587-92.
    PMID: 14692708
    INTRODUCTION: Arterial stiffness is emerging as a useful index of vascular health. Postmenopausal women have been shown to have stiffer arteries. Hormone replacement therapy and soy isoflavones improve arterial stiffness in these women. The aim of this study is to establish whether vitamin E improves arterial stiffness in postmenopausal women after 10 weeks of supplementation.

    METHODS: Twenty postmenopausal women with a mean age of 54.59 +/- 1.22 years participated in this randomized, crossover, double-blind, placebo-controlled clinical trial. All women received 400 IU of tocopherol daily for 10 weeks or a placebo capsule, before being crossed over for treatment. At intervals of 5 weeks, subjects attended sessions where measurements of arterial stiffness, blood pressure and plasma vitamin E level were taken. Pulse wave velocity measurement, using the automated Complior machine, was used as an index of arterial stiffness.

    RESULTS: Plasma vitamin E level was 30.38 +/- 1.56 micromol/l at baseline, after treatment it was 59.01 +/- 3.30 micromol/l and 31.17 +/- 1.37 micromol/l with vitamin E and placebo, respectively (p < 0.001). There was no significant difference in pulse wave velocity after 10-week treatment with placebo and vitamin E (9.14 +/- 0.29 versus 9.04 +/- 0.29 m/s, respectively). Similarly, no difference in systolic and diastolic blood pressure was seen between placebo and vitamin E at the end of 10 weeks.

    CONCLUSION: Supplementary vitamin E for 10 weeks at 400 IU daily has no effect on arterial stiffness in healthy postmenopausal women.

  2. Zabidi MS, Abu Bakar R, Musa N, Mustafa S, Wan Yusuf WN
    Pharmaceuticals (Basel), 2021 Sep 06;14(9).
    PMID: 34577603 DOI: 10.3390/ph14090903
    Understanding the pharmacokinetics parameter of colistin methanesulfonate sodium (CMS) and colistin is needed to optimize the dosage regimen in critically ill patients. However, there is a scarcity of pharmacokinetics parameters in this population. This review provides a comprehensive understanding of CMS and colistin pharmacokinetics parameters in this population. The relevant studies published in English that reported on the pharmacokinetics of CMS and colistin from 2000 until 2020 were systematically searched using the PubMed and Scopus electronic databases. Reference lists of articles were reviewed to identify additional studies. A total of 252 citation titles were identified, of which 101 potentially relevant abstracts were screened, and 25 full-text articles were selected for detailed analysis. Of those, 15 studies were included for the review. This review has demonstrated vast inter-study discrepancies in colistin plasma concentration and the pharmacokinetics parameter estimates. The discrepancies might be due to complex pathophysiological changes in the population studied, differences in CMS brand used, methodology, and study protocol. Application of loading dose of CMS and an additional dose of CMS after dialysis session was recommended by some studies. In view of inter-patient and intra-patient variability in colistin plasma concentration and pharmacokinetics parameters, personalized colistin dosing for this population is recommended.
  3. Mustafa S, Hassan NB, Tan SC, Ab Rahman AK, Low LL, Wan Yusuf WN
    Turk J Med Sci, 2016 Dec 20;46(6):1875-1881.
    PMID: 28081342 DOI: 10.3906/sag-1503-116
    BACKGROUND/AIM: Nevirapine is a reverse-transcriptase inhibitor widely used in combination therapy to treat HIV infection. Nevirapine is extensively metabolized in the liver and CYP2B6 is mainly responsible for oxidation of 3-hydroxynevirapine (3-OH NVP). This study aims to explore CYP2B6 activity by measuring 2-hydroxynevirapine (2-OH NVP) and 3-OH NVP in plasma and to identify factors associated with nevirapine pharmacokinetic parameters.

    MATERIALS AND METHODS: A total of 112 patients were recruited and treated with nevirapine-based antiretroviral therapy. Plasma nevirapine and metabolite concentrations were assayed using high-performance liquid chromatography via liquid-liquid extraction.

    RESULTS: Thirty-nine (34.8%) of the patients had no 3-OH NVP detected in their plasma while 2-OH NVP was detected in all patients. Metabolite concentrations were low compared to nevirapine. Positive correlations were observed between nevirapine and its metabolites, 2-OH NVP (P < 0.01) and 3-OH NVP (P = 0.012). Nevirapine concentration was decreased when concomitantly administered with methadone. Univariate analysis showed that ALT level, AST level, and detection of 3-OH NVP were associated with nevirapine pharmacokinetic parameters.

    CONCLUSION: The variability of nevirapine pharmacokinetic parameters was caused by liver enzymes and the presence of 3-OH NVP metabolites. The presence of 3-OH NVP can probably be used to distinguished CYP2B6 activity and efficacy of nevirapine in patients with HIV infection.

  4. Wan Yusuf WN, Wan Mohammad WMZ, Gan SH, Mustafa M, Abd Aziz CB, Sulaiman SA
    J Tradit Complement Med, 2019 Oct;9(4):249-256.
    PMID: 31453119 DOI: 10.1016/j.jtcme.2018.05.003
    This is the first study to report on the effects of honey in asymptomatic HIV positive subjects in ameliorating CD4 count, viral load (VL) and quality of life (QOL). It is a randomized, controlled, open labelled study, comparing the effects of Tualang honey (TH) administration for six months at three different doses: 20 g (THL), 40 g (THI) or 60 g (THH) daily compared with control (no administered treatment, THC). Only asymptomatic HIV positive subjects (n=95) having CD4 count 250-600 cell/ml, not on antiretrovirals were enrolled. Blood, (together with QOL questionnaires administration) were investigated at baseline, three and six months (CD4 cell count) while VL was determined only at baseline and six months. Significant reductions in CD4 counts in THL and THC groups (p= 0.003 for both) were seen with no significant reductions in the CD4 counts in THI and THH groups (p=0.447 and 0.053 respectively). There was improvement in VL in THC and THI (130% and 32% respectively) and reductions in THL and THH (26% and 8% respectively). Within and between group analyses for VL indicated significant differences between THL and THH compared to THC. In addition, significant improvement in QOL of groups which received TH was noted. TH has the potential to improve the QOL (physical and psychological) and CD4 counts. There was a trend of lower VL in asymptomatic HIV subjects following TH administration thus supporting the possible role of TH in boosting the immune system by improving CD4 counts, causing VL reductions in HIV positive subjects.
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