OBJECTIVES: This study aimed to compare the QTc interval between low and high dose methadone groups and evaluate the pattern of QTc variation.
METHODS: This is a prospective cohort study conducted from December 2010 till August 2011 at Malaysian University of Science's Hospital. Forty six subjects, grouped in high dose (>80mg) and low dose (<80mg) oral methadone, were followed-up at 4-weekly for QTc measurements. Relevant demographic and biochemical profiles were taken at intervals with concurrent QTc measurements.
RESULTS: No significant QTc differences between methadone dosage groups were found at Week 0 (434ms vs 444ms, p = 0.166) and week 8 (446.5ms vs 459ms, p = 0.076), but not at week 4(435ms vs 450ms, p = 0.029). However, there were significant associations between the groups with QTc prolongation at week 0 and 4 (OR 4.29(95% CI 1.01, 18.72) p=0.044 and OR 5.18 (95% CI 1.34, 20.06) p =0.013, respectively) but not at week 8 (OR 2.44 (95% CI 0.74, 8.01) p=0.139). On multivariate analysis, dose group was the sole significant factor for QTc prolongation for week 0 and 4 (p values 0.047 and 0.017, respectively), but not at week 8.
CONCLUSION: High-dose methadone group is more likely to develop prolonged QTc than low-dose group. However, such effects were inconsistent and occurred even during chronic methadone therapy, mandating judicious QTc and serum methadone monitoring.
KEYWORDS: High Dose; Low Dose; Methadone; QTc
Colorectal cancer (CRC) remains one of the major leading causes of cancer related morbidity and mortality. Apart from the conventional anti-neoplastic agents, metformin, a biguanide anti-diabetic agent, has recently found to have anti-cancer property. Several studies observed the effect of metformin towards its anti-cancer effect on colon or colorectal cancer in diabetic patients. However, only a few studies showed its effect on colorectal cancer in relation to the non-diabetic status. The present review aimed to highlight the insight into the molecular pathway of metformin towards colorectal cancer in the absence of diabetes mellitus. In CRC-independent of diabetes mellitus, highly deregulation of PI3K/AKT pathway is found which activates the downstream mammalian target of rapamycin (mTOR). Metformin inhibits cancer growth in colon by suppressing the colonic epithelial proliferation by inhibiting the mTOR pathway. Metformin exerts its anti-neoplastic effects by acting on tumour suppressor pathway via activating the adenosine monophosphate.activated protein kinase (AMPK) signaling pathway. Metformin interrupts the glucose metabolism by activating the AMPK. Metformin reduces tumour cell growth and metastasis by activating the p53 tumour suppressor gene. In addition to its therapeutic benefits, metformin is easily accessible, cost effective with better tolerance to the patients compared to the chemotherapeutic agents. This review summarised modern findings on the therapeutic applications of metformin on the colorectal cancer with no evidences of diabetes mellitus.