METHODS: Warfarin relies on regular monitoring of International Normalized Ratio which is a standardized test to measure prothrombin time and appropriate dose adjustment. Pharmacometabonomics is a novel scientific field which deals with identification and quantification of the metabolites present in the metabolome using spectroscopic techniques such as Nuclear Magnetic Resonance (NMR). Pharmacometabonomics helps to indicate perturbation in the levels of metabolites in the cells and tissues due to drug or ingestion of any substance. NMR is one of the most widely-used spectroscopic techniques in metabolomics because of its reproducibility and speed.
RESULTS: There are many factors that influence the metabolism of warfarin, making changes in drug dosage common, and clinical factors like drug-drug interactions, dietary interactions and age explain for the most part the variability in warfarin dosing. Some studies have showed that pharmacogenetic testing for warfarin dosing does not improve health outcomes, and around 26% of the variation in warfarin dose requirements remains unexplained yet.
CONCLUSION: Many recent pharmacometabonomics studies have been conducted to identify novel biomarkers of drug therapies such as paracetamol, aspirin and simvastatin. Thus, a technique such as NMR based pharmacometabonomics to find novel biomarkers in plasma and urine might be useful to predict warfarin outcome.
METHOD: This retrospective study involved SLE patients who attended the Rheumatology Clinic at the Hospital Kuala Lumpur from January 2014 to December 2016. Vitamin D was categorised as normal, insufficient or deficient, and the clinical variables were compared across vitamin D categories with chi-squared tests and Pearson correlation coefficient.
RESULTS: We included 216 patients. The mean 25(OH)D concentration was 51.3(Standard Deviation; SD 14.8) nmol/L. Fifty (23.1%) patients had vitamin D deficiency, 120 (55.6%) had vitamin D insufficiency, while 46 (21.3%) had adequate vitamin D levels. There were statistically significant associations between vitamin D status and ethnic group, lupus nephritis and hypertension. No correlations were observed between vitamin D status with SLEDAI score (Pearson correlation coefficient -0.015, p=0.829) as well as SDI score (Pearson correlation coefficient -0.017, p=0.801).
CONCLUSION: SLE patients should be screened for vitamin D concentrations and their levels optimised.
Materials and Methods: TQ-NLC was radiolabeled with technetium-99m before the administration to the rats. The biodistribution and pharmacokinetics parameters were then evaluated at various time points. The rats were imaged at time intervals and the percentage of the injected dose/gram (%ID/g) in blood and each organ was analyzed.
Results: Oral administration of TQ-NLC exhibited greater relative bioavailability compared to intravenous administration. It is postulated that the movement of TQ-NLC through the intestinal lymphatic system bypasses the first metabolism and therefore enhances the relative bioavailability. However, oral administration has a slower absorption rate compared to intravenous administration where the AUC0-∞ was 4.539 times lower than the latter.
Conclusion: TQ-NLC had better absorption when administered intravenously compared to oral administration. However, oral administration showed greater bioavailability compared to the intravenous route. This study provides the pharmacokinetics and biodistribution profile of TQ-NLC in vivo which is useful to assist researchers in clinical use.
RESULTS: No significant difference in plasma propranolol (mean +/- SEM) levels was seen between races six hours after the last dose (Malays, 59.7 +/- 8.8 ng/ml, Indians, 67.6 +/- 19.3 ng/ml, Chinese, 58.4 +/- 7.9 ng/ml). Chinese were least sensitive to the bradycardic and hypotensive effects of propranolol at rest and exercise. Indians and Malays had significant reduction of supine systolic blood pressure with propranolol but not Chinese. Comparison of percentage reductions of systolic blood pressure at supine, sitting and exercise by repeated measure analysis showed the Malays to have significantly higher change compared to the Chinese (p = 0.022). Similarly, comparison of percentage reductions of heart rate at supine, sitting and exercise by repeated measure analysis showed the Malays to have significantly higher change compared to the Chinese (p = 0.040). Average change in potassium concentrations at peak exercise and recovery showed the Indians to have significantly higher increase in potassium levels with propranolol compared to the Malays (p = 0.038). However, no significant interethnic difference was seen in the reduction of glucose levels at rest, peak exercise or recovery. Also, no significant interethnic difference was seen in reduction of FEV1 values.
CONCLUSION: We, therefore, conclude that ethnic differences in response to blockade of beta-receptors exist among racial groups in Malaysia. These differences were seen at similar plasma drug levels between races suggesting ethnic differences in drug sensitivity, rather than differences in drug disposition.