Biomedical subjects

S H Gan

Publications and source records attributed to S H Gan.

8 recordsLinked to original sources

PubMed2006

PharmGED: Pharmacogenetic Effect Database.

Prediction and elucidation of pharmacogenetic effects is important for facilitating the development of personalized medicines. Knowledge of polymorphism-induced and other types of drug-response variations is needed for facilitating such studies. Although databases of pharmacogenetic knowledge, polymorphism and toxicogenomic information have appeared, some of the relevant data are provided in separate web-pages and in terms of relatively long descriptions quoted from literatures. To facilitate easy and quick assessment of the relevant information, it is helpful to develop databases that provide all of the information related to a pharmacogenetic effect in the same web-page and in brief descriptions. We developed a database, Pharmacogenetic Effect Database (PharmGED), for providing sequence, function, polymorphism, affected drugs and pharmacogenetic effects. PharmGED can be accessed at http://bidd.cz3.nus.edu.sg/phg/ free of charge for academic use. It currently contains 1825 entries covering 108 disease conditions, 266 distinct proteins, 693 polymorphisms, 414 drugs/ligands cited from 856 references.

Animals↗

PubMed2004

Relationship between Type A and B personality and debrisoquine hydroxylation capacity.

AIM: 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. METHODS: Type A and B personality questionnaires were administered to 48 healthy patients undergoing elective orthopaedic surgery. After obtaining informed consent, patients were genotyped for the various CYP2D6 alleles by allele-specific polymerase chain reaction. Based on the genotypes, patients were grouped as extensive metabolizer (EM)1 (normal) (CYP2D6*1/*1), EM2 (intermediate) (CYP2D6*1/*4, CYP2D6*1/*5, CYP2D6*1/*9 and CYP2D6*1/*10) and EM3 (slow) (CYP2D6*4/*10, CYP2D6*5/*10, CYP2D6*10/*10 and CYP2D6*10/*17). Chi(2) was used to determine the relationship between the groups and personality types. RESULTS: The percentages of patients who were of the EM1, EM2 and EM3 groups were 20.8%, 52.1% and 27.1%, respectively. There was a significant difference (P = 0.032) between the three groups in terms of personality type, in which EM1 showed a tendency to be of personality Type A while EM2 and EM3 tended to be of personality Type B. CONCLUSION: The study suggests that there is a relationship between CYP2D6 activity and Type A and B personality.

Adolescent↗

PubMed2004

Population pharmacokinetic modelling of tramadol with application of the NPEM algorithms.

BACKGROUND AND OBJECTIVE: 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. METHODS: The parametric Iterative Two-stage Bayesian Population Model (IT2B) program followed by the Non-parametric Expectation Maximization Population Model (NPEM2) program was used to determine population pharmacokinetic parameter values of tramadol in 138 postoperative orthopaedic Malaysian patients. All patients had received a 100 mg intravenous dose of tramadol, infused over 2-3 min, as their first postoperative analgesic. Blood was sampled at 0 min and subsequently at 15, 30 min, 1, 2, 4, 8, 16, 20 and 24 h for serum tramadol high-performance liquid chromatography analysis. RESULTS AND DISCUSSION: The one-compartmental model pharmacokinetic parameters--volume of distribution (Vd), elimination rate constant (kel) and the total clearance rates (ClT)--found were: mean Vd = 167.6 +/- 63.84 L; median Vd = 161.48 L; mean kel = 0.1241 +/- 0.056 h(-1); median kel = 0.1138 h(-1); ClT = 19.57 +/- 9.51 L/h; median ClT =18.12 L/h. The interindividual coefficient of variation of ClT (48.56%) was higher than that of Vd (38.09%), indicating the presence of other possible influencing factors on tramadol's ClT such as CYP2D6 polymorphism, gender and age. Overall, NPEM2 suggested more diversity in the population than did IT2B.

Adolescent↗

PubMed2003

Standard CYP2D6 genotyping procedures fail for the CYP2D6*5 and duplication alleles when hair roots are used as a source of DNA.

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.

Alleles↗

PubMed2002

Correlation of tramadol pharmacokinetics and CYP2D6*10 genotype in Malaysian subjects.

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.

Adolescent↗

PubMed2002

Method development and validation of a high-performance liquid chromatographic method for tramadol in human plasma using liquid-liquid extraction.

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.

Analgesics, Opioid↗

PubMed2001

Validation of a high-performance liquid chromatography method for tramadol and o-desmethyltramadol in human plasma using solid-phase extraction.

An HPLC system using solid-phase extraction and HPLC with UV detection has been validated in order to determine tramadol and o-desmethyltramadol (M1) concentrations in human plasma. The method developed was selective and linear for concentrations ranging from 50 to 3,500 ng/ml (tramadol) and 50 to 500 ng/ml (M1) with mean recoveries of 94.36 +/- 12.53% and 93.52 +/- 7.88%, respectively. Limit of quantitation (LOQ) was 50 ng/ml. For tramadol, the intra-day accuracy ranged from 95.48 to 114.64% and the inter-day accuracy, 97.21 to 103.24%. Good precision (0.51 and 18.32% for intra- and inter-day, respectively) was obtained at LOQ. The system has been applied to determine tramadol concentrations in human plasma samples for a pharmacokinetic study.

Analgesics, Opioid↗

PubMed1991

Silent myocardial ischaemia: the Tan Tock Seng experience.

The results of treadmill exercise stress test (TMX) for ischaemia is based on ST-segment depression. Patients with positive test may or may not be symptomatic. This study examines if there are any differences between these two groups of patients. A total of thirty-nine patients with coronary artery disease and positive TMX results in 1988 was studied. There were 16 patients with chest pain and 23 without. They were followed-up for a mean period of 16.9 and 15.2 months respectively. The following factors were found not to be statistically significant between these two groups of patients: age, sex, race, height, weight, history of hypertension, diabetes mellitus or smoking, indication for the test, use of drugs, total and HDL-cholesterol, exercise duration and the initial double product. The difference between the maximal double product of the two groups was statistically significant (p = 0.004). In the follow-up period, in the group of patients with silent myocardial ischaemia, one had a cardiac event and one underwent revascularisation. While in the symptomatic group, two had cardiac events and seven underwent revascularisation. There were no deaths in either group. The difference in overall outcome was significant statistically (p = 0.002). Therefore, patients with silent myocardial ischaemia have a higher maximal double product in TMX; hence a higher maximal workload and a less adverse outcome compared to symptomatic patients.

Coronary Disease↗