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  1. Ibrahim Zubil, AR., Wan Adnan W. A
    MyJurnal
    Occupational health hazards as a result to exposure to mineral dust containing silica has been established long time ago in occupational health history. Its effects on lung function and symptom was evaluated in a cross sectional studied among 49 small enterprise pottery workers in the county of Sayong clustered in 3 villages. Respiratory symptoms and lung function was evaluated using MRC respiratory questionnaire 86 and standard spirometry performed. The prevalence of chronic cough, phlegm and chest tightness was 24.5%, 16% and16% respectively. There was no significant decrement in lung function parameters from the predicted normal value with the mean predicted FVC; FEV1 and FEV1/FVC ratio was 85.32%, 83.87% and 99.22 respectively. The relationship between lung symptoms and lung function parameters was evaluated and the result was not significant.
  2. Gan SH, Ismail R, Wan Adnan WA, Zulmi W, Jelliffe RW
    J Clin Pharm Ther, 2004 Oct;29(5):455-63.
    PMID: 15482390
    Although the kinetic behaviour of tramadol has been described, the present study is the first to our knowledge, to report specifically on the population pharmacokinetic modelling of tramadol hydrochloride.
  3. Gan SH, Ismail R, Wan Adnan WA, Wan Z
    J Pharm Biomed Anal, 2002 Sep 05;30(2):189-195.
    PMID: 12191703
    The aim of the present study is to investigate the influence of the CYP2D6*10 allele on the disposition of tramadol hydrochloride in Malaysian subjects. A single dose of 100 mg tramadol was given intravenously to 30 healthy orthopaedic patients undergoing various elective surgeries. After having obtained written informed consents, patients were genotyped for CYP2D6*10: the most common CYP2D6 allele among Asians by means of allele-specific polymerase chain reaction. The presence of other mutations (CYP2D6*1, *3, *4, *5, *9 and *17) was also investigated. Tramadol was extracted from 1 ml serum with an n-hexane: ethylacetate combination (4:1) after alkalinisation with ammonia (pH 10.6). Serum concentrations were measured by means of high-performance liquid chromatography. The pharmacokinetics of tramadol was studied during the 24 h after the dose. As among other Asians, the allele frequency for CYP2D6*10 among Malaysians was high (0.43). Subjects who were homozygous for CYP2D6*10 had significantly (P=0.046) longer mean serum half-life of tramadol than subjects of the normal or the heterozygous group (Kruskal-Wallis test). When patients were screened for the presence of other alleles, the pharmacokinetic parameter values were better explained. CYP2D6 activity may play a main role in determining tramadol pharmacokinetics. The CYP2D6*10 allele particularly was associated with higher serum levels of tramadol compared with the CYP2D6*1 allele. However, genotyping for CYP2D6*10 alone is not sufficient to explain tramadol disposition.
  4. Gan SH, Ismail R, Wan Adnan WA, Wan Z
    Clin Chim Acta, 2003 Mar;329(1-2):61-8.
    PMID: 12589966 DOI: 10.1016/s0009-8981(03)00019-6
    BACKGROUND: Hair roots provide a useful alternative to blood as a source of DNA for genotyping. Besides simple and non-invasive collections, the DNA extraction step is also easy to perform and is fast. The aim of our study is to determine if hair roots can be used to genotype all of the common CYP2D6 alleles for routine screening purposes.

    METHOD: The study complies with the Declaration of Helsinki. After obtaining informed consents, both blood and hair samples were collected from 92 patients for genotyping of the CYP2D6 gene. PCR was used to detect the following mutations: CYP2D6*1, *3, *4, *5, *9, *10, *17 and duplication gene. The results were compared where hair roots and blood were used as templates for DNA respectively.

    RESULTS: When blood was used as a source of DNA for genotyping, all of the investigated CYP2D6 alleles were successfully amplified. However, with hair roots, the genes with the larger fragment sizes: CYP2D6*5 and the duplication gene could not be amplified and the bands of other alleles investigated were faint when visualized under UV light.

    CONCLUSIONS: DNA extraction from hair roots and leucocytes yielded similar results but the DNA extracted from hair roots did not allow successful amplification of the longer genes such as the CYP2D6*5 and the duplication gene.
  5. Gan SH, Ismail R, Wan Adnan WA, Wan Z
    PMID: 12016023
    An HPLC system using a simple liquid-liquid extraction and HPLC with UV detection has been validated to determine tramadol concentration in human plasma. The method developed was selective and linear for concentrations ranging from 10 to 2000 ng/ml with average recovery of 98.63%. The limit of quantitation (LOQ) was 10 ng/ml and the percentage recovery of the internal standard phenacetin was 76.51%. The intra-day accuracy ranged from 87.55 to 105.99% and the inter-day accuracy, 93.44 to 98.43% for tramadol. Good precision (5.32 and 6.67% for intra- and inter-day, respectively) was obtained at LOQ. The method has been applied to determine tramadol concentrations in human plasma samples for a pharmacokinetic study.
  6. 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.
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