Displaying publications 1 - 20 of 34 in total

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  1. Kua KP, Lee SW
    Br J Clin Pharmacol, 2017 01;83(1):180-191.
    PMID: 27526255 DOI: 10.1111/bcp.13089
    AIMS: This study evaluated the therapeutic outcomes of early versus late caffeine therapy in preterm neonates.

    METHODS: We performed a systematic literature search in PubMed, Embase, CINAHL and CENTRAL from inception to 30 June 2016 to identify studies investigating the use of early caffeine therapy (initiated at less than 3 days of life) in preterm infants. Effect estimates were combined using random-effects meta-analysis. The primary outcomes for this study were bronchopulmonary dysplasia and mortality.

    RESULTS: The initial search found 4066 citations, of which 14 studies enrolling a total of 64 438 participants were included. The time of initiation of early caffeine therapy varied from the first 2 h to 3 days postnatal. Early caffeine therapy reduced the risk of bronchopulmonary dysplasia in both cohort studies (RR: 0.80, 95% CI: 0.66 to 0.96) and randomized controlled trials (RR: 0.67, 95% CI: 0.56 to 0.81). In cohort studies, neonates treated early with caffeine also showed decreased risks of patent ductus arteriosus, brain injury, retinopathy of prematurity and postnatal steroid use. However, the mortality rate was increased.

    CONCLUSIONS: The findings suggest that early caffeine therapy is associated with reduced incidence of bronchopulmonary dysplasia and may help decrease the burden of morbidities in preterm infants.

  2. Akram Z, Abduljabbar T, Kellesarian SV, Abu Hassan MI, Javed F, Vohra F
    Br J Clin Pharmacol, 2017 03;83(3):444-454.
    PMID: 27718252 DOI: 10.1111/bcp.13147
    AIMS: The aim of this systematic review was to assess the efficacy of bisphosphonate therapy as an adjunct to scaling and root planing (SRP) in the management of periodontitis.

    METHODS: Databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Cochrane Oral Health Group Trials Register databases) were searched up to and including July 2016. The primary outcome was probing depth (PD), and the secondary outcomes were changes in clinical attachment level (CAL) and bone defect (BD) fill. The mean differences (MD) of outcomes and 95% confidence intervals (CI) for each variable were calculated using random effect model.

    RESULTS: Eight clinical studies were included. Seven studies used alendronate as an adjunct to SRP; of these, four studies used topical application and three used oral alendronate. Considering the effects of adjunctive bisphosphonates as compared to SRP alone, a high degree of heterogeneity for PD (Q value = 39.6, P 

  3. Kamal MA, Smith PF, Chaiyakunapruk N, Wu DBC, Pratoomsoot C, Lee KKC, et al.
    Br J Clin Pharmacol, 2017 07;83(7):1580-1594.
    PMID: 28176362 DOI: 10.1111/bcp.13229
    AIMS: A modular interdisciplinary platform was developed to investigate the economic impact of oseltamivir treatment by dosage regimen under simulated influenza pandemic scenarios.

    METHODS: The pharmacology module consisted of a pharmacokinetic distribution of oseltamivir carboxylate daily area under the concentration-time curve at steady state (simulated for 75 mg and 150 mg twice daily regimens for 5 days) and a pharmacodynamic distribution of viral shedding duration obtained from phase II influenza inoculation data. The epidemiological module comprised a susceptible, exposed, infected, recovered (SEIR) model to which drug effect on the basic reproductive number (R0 ), a measure of transmissibility, was linked by reduction of viral shedding duration. The number of infected patients per population of 100 000 susceptible individuals was simulated for a series of pandemic scenarios, varying oseltamivir dose, R0 (1.9 vs. 2.7), and drug uptake (25%, 50%, and 80%). The number of infected patients for each scenario was entered into the health economics module, a decision analytic model populated with branch probabilities, disease utility, costs of hospitalized patients developing complications, and case-fatality rates. Change in quality-adjusted life years was determined relative to base case.

    RESULTS: Oseltamivir 75 mg relative to no treatment reduced the median number of infected patients, increased change in quality-adjusted life years by deaths averted, and was cost-saving under all scenarios; 150 mg relative to 75 mg was not cost effective in low transmissibility scenarios but was cost saving in high transmissibility scenarios.

    CONCLUSION: This methodological study demonstrates proof of concept that the disciplines of pharmacology, disease epidemiology and health economics can be linked in a single quantitative framework.

  4. Chong KT, Ho WF, Koo SH, Thompson P, Lee EJ
    Br J Clin Pharmacol, 2007 Mar;63(3):328-32.
    PMID: 16981896
    To determine and compare the distribution of the FcgammaRIIIa 176 F/V polymorphism across three ethnically distinct populations (Chinese, Asian Indians and Malays) in Singapore.
  5. Koo SH, Ho WF, Lee EJ
    Br J Clin Pharmacol, 2006 Mar;61(3):301-8.
    PMID: 16487223
    To determine the genetic variability of long QT syndrome (LQTS)-associated genes (KCNQ1, HERG, KCNE1 and KCNE2) among three distinct ethnic groups in the Singapore population.
  6. Pang YS, Yang YS, Wong LP, Lee TC, Mustafa AM, Mohamed Z, et al.
    Br J Clin Pharmacol, 2004 Sep;58(3):332-5.
    PMID: 15327595
    Impaired S-mephenytoin 4'-hydroxylation is a well-described genetic polymorphism affecting drug metabolism in humans. Although ethnic differences in its distribution of polymorphism has been described, it is not known whether there is an ethnic heterogeneity of the structure and expression of the CYP2C19 enzyme in the Malaysian population.
  7. Gan SH, Ismail R, Wan Adnan WA, Zulmi W, Kumaraswamy N, Larmie ET
    Br J Clin Pharmacol, 2004 Jun;57(6):785-9.
    PMID: 15151524
    A person with Type A personality is an 'aggressor' compared with the rarely harried Type B. Although debrisoquine hydroxylase (CYP2D6) capacity has been associated with personality, no study has specifically investigated its association with personality Type A and B. Therefore the aim of this research was to study the impact of CYP2D6 on Type A and B personality.
  8. Lang CC, Jamal SK, Mohamed Z, Mustafa MR, Mustafa AM, Lee TC
    Br J Clin Pharmacol, 2003 Jun;55(6):588-90.
    PMID: 12814453
    AIMS: Nafcillin (Wyeth Laboratories, Philadelphia, PA, USA) has been reported to induce the metabolism of cyclosporin and warfarin, which are known substrates of cytochrome P-450 (CYP). However, there has not been any report to date on its possible interaction with nifedipine, an index substrate of the enzyme, CYP3A4.

    METHODS: Nine healthy normotensive subjects participated in this randomized placebo-controlled two-way crossover study examining the effects of 5 days' pretreatment of nafcillin 500 mg or placebo four times daily on the pharmacokinetics of an oral dose of nifedipine 10 mg. Plasma nifedipine concentrations were measured by gas chromatography-mass spectro.

    RESULTS: The area under the plasma nifedipine concentration-time curve (AUC0-alpha) in nafcillin-pretreated subjects (80.9 +/- 32.9 micro g l-1 h-1) was significantly decreased compared with subjects who received only nifedipine (216.4 +/- 93.2 micro g l-1 h-1) (P < 0.001). Total plasma clearance of nifedipine (CL/F) was significantly increased with nafcillin pretreatment (138.5 +/- 42.0 l h-1 vs 56.5 +/- 32.0 l h-1) (P < 0.002).

    CONCLUSIONS: The results show that nafcillin pretreatment markedly increased the clearance of nifedipine and suggest that nafcillin is a potent inducer of CYP enzyme.

  9. Abd Rahman AN, Tett SE, Abdul Gafor HA, McWhinney BC, Staatz CE
    Br J Clin Pharmacol, 2015 Nov;80(5):1064-75.
    PMID: 25959850 DOI: 10.1111/bcp.12678
    AIMS: The aim was to examine relationships between total and unbound mycophenolic acid (MPA) and prednisolone exposure and clinical outcomes in patients with lupus nephritis.
    METHODS: Six blood samples were drawn pre- and at 1, 2, 4, 6 and 8 h post-dose and total and unbound MPA and prednisolone pre-dose (C0 ), maximum concentration (Cmax ) and area under the concentration-time curve (AUC) were determined using non-compartmental analysis in 25 patients. The analyses evaluated drug exposures in relation to treatment response since starting MPA and drug-related adverse events.
    RESULTS: Dose-normalized AUC varied 10-, 8-, 7- and 19-fold for total MPA, unbound MPA, total prednisolone and unbound prednisolone, respectively. Median values (95% CI) of total MPA AUC(0,8 h) (21.5 [15.0, 42.0] vs. 11.2 [4.8, 30.0] mg l(-1) h, P= 0.048) and Cmax (11.9 [6.7, 26.3] vs. 6.1 [1.6, 9.2] mg l(-1) , P = 0.016) were significantly higher in responders than non-responders. Anaemia was significantly associated with higher total (37.8 [14.1, 77.5] vs. 18.5 [11.7, 32.7] mg l(-1) h, P = 0.038) and unbound MPA AUC(0,12 h) (751 [214, 830] vs. 227 [151, 389] mg l(-1) h, P = 0.004). Unbound prednisolone AUC(0,24 h) was significantly higher in patients with Cushingoid appearance (unbound: 1372 [1242, 1774] vs. 846 [528, 1049] nmol l(-1) h, P = 0.019) than in those without. Poorer treatment response was observed in patients with lowest tertile exposure to both total MPA and prednisolone as compared with patients with middle and higher tertile exposure (17% vs. 74%, P = 0.023).
    CONCLUSIONS: This study suggests a potential role for therapeutic drug monitoring in individualizing immunosuppressant therapy in patients with lupus nephritis.
    KEYWORDS: lupus nephritis; mycophenolic acid; pharmacodynamics; pharmacokinetics; prednisolone; treatment outcome
    Study site: Nephrology and SLE Clinics, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
  10. Hatah E, Braund R, Tordoff J, Duffull SB
    Br J Clin Pharmacol, 2014 Jan;77(1):102-15.
    PMID: 23594037 DOI: 10.1111/bcp.12140
    The aim was to examine the impact of fee-for-service pharmacist-led medication review on patient outcomes and quantify this according to the type of review undertaken, e.g. adherence support and clinical medication review.
  11. Zaharan NL, Williams D, Bennett K
    Br J Clin Pharmacol, 2013 Apr;75(4):1118-24.
    PMID: 22845189 DOI: 10.1111/j.1365-2125.2012.04403.x
    (i) To examine the incidence of new onset treated diabetes in patients treated with different types of statins and (ii) the relationship between the duration and dose of statins and the subsequent development of new onset treated diabetes.
  12. Hassan NB, Ismail HC, Naing L, Conroy RM, Abdul Rahman AR
    Br J Clin Pharmacol, 2010 Oct;70(4):500-13.
    PMID: 20840442 DOI: 10.1111/j.1365-2125.2009.03597.x
    The aims were to develop and validate a new Prescription Quality Index (PQI) for the measurement of prescription quality in chronic diseases.
  13. 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.

  14. Sim SM, Back DJ, Breckenridge AM
    Br J Clin Pharmacol, 1991 Jul;32(1):17-21.
    PMID: 1909542
    1. Zidovudine (3'-azido-3'-deoxythymidine; AZT) is the drug of proven efficacy available for the treatment of patients with AIDS or ARC. It is eliminated mainly by hepatic glucuronidation. Therefore, interference with this metabolic pathway may lead to enhancement of AZT effect or to increased toxicity of the drug. We have examined the effect of a number of drugs which themselves undergo glucuronidation on AZT conjugation by human liver microsomes in vitro. 2. AZT glucuronidation followed Michaelis-Menten kinetics. The apparent Km and Vmax values (mean +/- s.d., n = 5), were 2.60 +/- 0.52 mM and 68.0 +/- 23.4 nmol h-1 mg-1, respectively, as determined from Eadie-Hofstee plots. 3. Dideoxyinosine, sulphanilamide and paracetamol were essentially non-inhibitory at concentrations up to 10 mM (4 times the concentration of AZT in the incubation). The most marked inhibitory effects were seen with indomethacin, naproxen, chloramphenicol, probenecid and ethinyloestradiol, with enzyme activity decreased by 97.7, 94.9, 88.7, 83.4% and 79.0%, respectively, at a concentration of 10 mM. Other compounds producing some inhibition of AZT conjugation were oxazepam, salicylic acid and acetylsalicylic acid. 4. Further studies are necessary to characterise the inhibition observed but the method described enables a screen of potentially important drug interactions to be carried out.
  15. Mansor SM, Navaratnam V, Mohamad M, Hussein S, Kumar A, Jamaludin A, et al.
    Br J Clin Pharmacol, 1989 Mar;27(3):381-6.
    PMID: 2785812
    A single dose pharmacokinetic study of a combined antimalarial formulation of mefloquine, sulphadoxine and pyrimethamine (Fansimef) has been performed in 10 healthy adult male Malaysian volunteers. The dose consisted of two tablets containing 250 mg mefloquine base, 500 mg sulphadoxine base and 25 mg pyrimethamine base each. Plasma concentrations of mefloquine and pyrimethamine were measured by GC-ECD, those of sulphadoxine by h.p.l.c. Time to peak concentrations (mean +/- s.d. for mefloquine (5.70 +/- 0.95 h), sulphadoxine (3.75 +/- 2.03 h) and pyrimethamine (3.30 +/- 1.98 h) were similar to those observed by others after administration of the single compounds. This was also true for elimination half-lives (t1/2). The t1/2s for mefloquine, sulphadoxine and pyrimethamine were 387 +/- 98 h, 255 +/- 61 h and 114 +/- 42 h, respectively.
  16. Jamaludin A, Mohamad M, Navaratnam V, Selliah K, Tan SC, Wernsdorfer WH, et al.
    Br J Clin Pharmacol, 1988 Feb;25(2):261-3.
    PMID: 3358888
    The hydrochloride, sulphate and ethylcarbonate salts of quinine were given in single oral doses (600 mg base equivalent) to nine healthy male subjects according to a cross-over design. No statistically significant differences were noted in the plasma drug concentration-time profiles although inter- and intra-subject variation in AUC, Cmax and tmax values was appreciable. The ethylcarbonate salt may be preferred for use in paediatric patients because of its neutral taste.
  17. Lee SW, Lai NM, Chaiyakunapruk N, Chong DW
    Br J Clin Pharmacol, 2017 01;83(1):172-179.
    PMID: 27081765 DOI: 10.1111/bcp.12976
    AIM: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common genetic disorder, affecting nearly 400 million individuals worldwide. Whilst it is known that a number of drugs, foods and chemicals can trigger haemolysis in G6PD deficient individuals, the association between herbal and dietary supplements and haemolysis is less clear. The objective of this study was to evaluate the association between herbal or dietary supplements and adverse events in G6PD deficient individuals.

    METHODS: We searched 14 electronic databases from their inception until November 2015 for articles describing the use of herbal or dietary supplements in G6PD deficient individuals. Additional publications were identified from manually searching textbooks, conference abstracts and the grey literature. All study designs were included as long as they contained clinical information. These gathered findings were summarized narratively.

    RESULTS: Thirty-two publications met inclusion criteria. These reported on 10 herbal and dietary supplements. Overall evidence linking haemolysis to a herbal/dietary supplement was only found for henna. No evidence of harm was observed for vitamin C, vitamin E, vitamin K, Gingko biloba and α-lipoic acid.

    CONCLUSIONS: The review showed that there was insufficient evidence to contravene the use of most herbal or dietary products at therapeutic doses in G6PD deficient subjects.

  18. Balan S, Hassali MA, Mak VS
    Br J Clin Pharmacol, 2015 Dec;80(6):1269-80.
    PMID: 26314841 DOI: 10.1111/bcp.12750
    AIM: The aim of this review was to provide an updated overview of awareness, knowledge and views of off-label prescribing in children.

    METHOD: A literature search using electronic databases including PubMed, Medline, Scopus, Science Direct, Springer Link, Proquest, Ebsco Host and Google Scholar was conducted. Additional articles were identified by reviewing the bibliography of retrieved articles. The articles were searched with any of the following medical subject headings (MeSH) terms in the title: attitude, awareness, knowledge, experience, view, off-label, pediatric, paediatric and children. The inclusion criteria were full text articles published in English between January 2004 and February 2015 and reported outcome related to awareness, knowledge and views regarding off-label prescribing in children. Editorials, reviews, notes, conference proceedings, letters and studies reporting prevalence of off-label prescribing were excluded. The articles were scrutinized using thematic analysis.

    RESULTS: Eleven studies conducted among doctors, community pharmacists, paediatric nurses, parents and children met the inclusion criteria. Nine themes were developed through document analysis which included main domains such as knowledge, awareness and views on off-label drug use in children, choice of information sources, reasons and suggestions to reduce off-label prescribing, concern regarding obtaining consent and participation in clinical trials.

    CONCLUSION: The studies reviewed reported that the majority of doctors and community pharmacists were familiar with the term off-label prescribing but knowledge among parents was low. Awareness on off-label prescribing in children remains low among all study participants. There is a mismatch between views on off-label prescribing in children of study participants and the finding of previous studies.

  19. Jiang N, Wang L, Xiang X, Li Z, Chiew EKH, Koo YM, et al.
    Br J Clin Pharmacol, 2021 Apr;87(4):1990-1999.
    PMID: 33037681 DOI: 10.1111/bcp.14596
    AIMS: Vincristine (VCR) is a key drug in the successful multidrug chemotherapy for childhood acute lymphoblastic leukaemia (ALL). However, it remains unclear how VCR pharmacokinetics affects its antileukaemic efficacy. The objective of this study is to explore the VCR pharmacokinetic parameters and intracellular VCR levels in an up-front window of Ma-Spore ALL 2010 (MS2010) study.

    METHODS: We randomised 429 children with newly diagnosed ALL to 15-minute vs 3-hour infusion for the first dose of VCR to study if prolonging the first dose of VCR infusion improved response. In a subgroup of 115 B-ALL and 20 T-ALL patients, we performed VCR plasma (n = 135 patients) and intracellular (n = 66 patients) pharmacokinetic studies. The correlations between pharmacokinetic parameters and intracellular VCR levels with early treatment response, final outcome and ABCB1 genotypes were analysed.

    RESULTS: There was no significant difference between 15-minute and 3-hour infusion schedules in median Day 8 peripheral or bone marrow blast response. Plasma VCR pharmacokinetic parameters did not predict outcome. However, in B-ALL, Day 33 minimal residual disease (MRD) negative patients and patients in continuous complete remission had significantly higher median intracellular VCR24h levels (P = .03 and P = .04, respectively). The median VCR24h intracellular levels were similar among the common genetic subtypes of ALL (P = .4). Patients homozygous for wild-type ABCB1 2677GG had significantly higher median intracellular VCR24h (P = .04) than 2677TT.

    CONCLUSION: We showed that in childhood B-ALL, the intracellular VCR24h levels in lymphoblasts affected treatment outcomes. The intracellular VCR24h level was independent of leukaemia subtype but dependent on host ABCB1 G2677T genotype.

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