Yow Shieng Uang

Effects of metformin dose on cancer risk reduction in patients with type 2 diabetes mellitus: A 6-year follow-up study

To explore the effects of metformin dose on cancer risk reduction in patients with type 2 diabetes.

Determination of caffeic acid in rabbit plasma by high-performance liquid chromatography.

A simple and sensitive high-performance liquid chromatographic method involving UV detection was developed for determination of caffeic acid in rabbit plasma. A Lichrosphere CN column (250 mm x 4 mm I.D., 5 microns) was used as the stationary phase and the mobile phase consisted of 2% acetic acid solution at a flow-rate of 1.0 ml/min. The UV absorbance was monitored at 320 nm. The plasma sample was acidified by the addition of 0.01 parts of concentrated phosphoric acid (85%) to maintain caffeic acid stability. After a simple clean-up procedure, the limit of quantitation achieved was 0.1 micrograms/ml, and the standard curve was found to be linear over the concentration ranges of 0.1-2.0 micrograms/ml and 0.1-40 micrograms/ml. The coefficient of variation for within- and between-run precision and accuracy was less than 10%, and the recovery was 82.3%.

A dose-dependent pharmacokinetic study on caffeic acid in rabbits after intravenous administration

The dose‐dependent pharmacokinetics of caffeic acid (CA) were studied in rabbits. Three different doses (5, 10, and 25 mg kg−1) were administered intravenously to six rabbits each. The concentration–time profiles for CA could be fitted by a two‐compartment model for each dose. The results showed that total‐body clearance and elimination rate constant from the central compartment (k10) after a 5 mg kg−1 dose were greater than those after the other two doses. Furthermore, the terminal elimination half‐life (β half‐life) and mean residence time (MRT) after a 5 mg kg−1 dose were less than after the other doses. The AUC value increased linearly with dose within the range of 10–25 mg kg−1. Most of the unchanged caffeic acid was excreted in the urine within 2 h. The percentage of unchanged caffeic acid excreted in the urine was 63·4, 60·0, and 55·4% after doses of 5, 10, and 25 mg kg−1, respectively, which was not significantly different. However, significant differences in the renal clearances and renal excretion rate constants were observed with a 5 mg kg−1 dose compared to the other doses. On the other hand, nonrenal clearances and nonrenal excretion rate constants showed no dose‐related differences. The differences observed in total‐body clearance, k10, β half‐life, and MRT between a 5 mg kg−1 dose and the other doses can be explained on the basis of the differences in renal clearance and renal excretion rate constants. ©1997 John Wiley & Sons, Ltd.

The use of proton pump inhibitors decreases the risk of diabetes mellitus in patients with upper gastrointestinal disease: A population-based retrospective cohort study

Objectives: The aim of this study was to investigate the effects of proton pump inhibitors (PPIs) on the risk of diabetes mellitus (DM) among patients with upper gastrointestinal disease (UGID). Methods: This was a retrospective cohort study with a follow-up period of 5 years. We identified 388,098 patients who were diagnosed with UGID between 2000 and 2006 from the Longitudinal Health Insurance Database of the Taiwan National Health Insurance program. We used Cox proportional hazard ratio (HR) to compare the risk of DM between UGID patients received PPIs and those did not receive PPIs. HRs were adjusted for possible confounders, including age, sex, hypertension, gout and/or hyperuricemia, coronary artery disease, stroke, pancreatitis, hyperlipidemia, obesity, H2-blocker use, and clozapine or olanzapine use. The dose-related effects of PPIs on the risk of DM were evaluated according to the defined daily dose (DDD). Results: The adjusted HR was 0.80 (95% CI, 0.73–0.88) for the study group (UGID patients with PPIs) compared with comparison group I (UGID patients without PPIs). Among patients who used PPIs, those older than 60 years of age had a lower risk of DM (HR, 0.73; 95% CI, 0.63–0.83) than those younger than 40 years. Additionally, the effect of PPIs was significantly dose-dependent (P for trend <0.001). Patients with UGID who received >540 DDDs of PPIs exhibited the greatest reduction in the risk of DM. Conclusions: Our results demonstrated a decreased risk of DM in UGID patients who used PPIs; the risk appeared to be significantly dose-dependent.

Allopurinol, benzbromarone and risk of coronary heart disease in gout patients: A population-based study.

BACKGROUND The effect of gout on the risk of developing coronary artery disease (CAD) is uncertain. Some studies have found that gout is a risk factor for acute myocardial infarction. This study examined the changes in risk of CAD in gout patients taking allopurinol and/or benzbromarone, and analyzed the dose-response relationship of both drugs with CAD incidence. METHODS The medical records of one million subjects from 2000 to 2011 were provided by the Taiwan National Health Insurance Research Database. Cox proportional hazard ratio was used to compare the risk of CAD in gout patients taking allopurinol or/and benzbromarone with those taking neither drug. Hazard ratios (HR) were adjusted for possible confounding factors, including age, gender, hypertension, hyperlipidemia, diabetes mellitus, chronic kidney disease, and relevant medications. RESULTS Of 8047 gout patients, 1422 were treated with allopurinol (Group A), 4141 with benzbromarone (Group B), and 2484 with both drugs (Group A/B) during the follow-up period. Our results showed the incidence of CAD after adjusting for covariates for Group A, Group B, and Group A/B did not significantly differ from the comparison group. However, after adjustment for covariates in dose-response analyses, treatment with over 270 defined daily doses (DDDs) of allopurinol, and over 360 DDDs of benzbromarone, was associated with a significantly reduced risk of CAD. CONCLUSION We found that the use of allopurinol and benzbromarone, whether alone or in combination, had a linear dose-response relationship between the numbers of defined daily doses and the risk of CAD, especially in higher DDDs.

Caffeic acid improves the bioavailability of l‐dopa in rabbit plasma

The impacts of caffeic acid (3,4‐dihydroxycinnamic acid, CA) on the pharmacokinetics of levodopa (L‐dopa) were studied in rabbits. A single dose of 5/1.25 mg·kg−1 l‐dopa/carbidopa was administered alone or was co‐administered with three different doses of caffeic acid (2.5, 5, and 10 mg·kg−1), or a single dose of 5 mg·kg−1 caffeic acid was administered alone via an intramuscular route to six rabbits each in a crossover treatment protocol. Plasma levels of l‐dopa, 3‐O‐methyldopa (3‐OMD), caffeic acid, and ferulic acid were determined and subsequently used to calculate their pharmacokinetic parameters. The results indicated that caffeic acid administered at a dose of 10 mg·kg−1 decreased about 22% of the peripheral formation of 3‐OMD and about 31% of the Cmax of 3‐OMD. In addition, the metabolic ratios (MR, AUC of 3‐OMD/AUC of L‐dopa) decreased by about 22%. Results also indicated that caffeic acid significantly decreased the proportion of 3‐OMD (p < 0.05). In contrast, the parameters of neither caffeic acid nor ferulic acid were significantly affected by l‐dopa/carbidopa. In conclusion, caffeic acid at a dose of 10 mg·kg−1 can significantly affect the COMT metabolic pathway of L‐dopa. Copyright

Determination of mephenoxalone in human plasma sample by high-performance liquid chromatography–fluorescence detection

A simple and sensitive high-performance liquid chromatographic method involving fluorescence detection was developed for the determination of mephenoxalone in human plasma. A Cosmosil 5C18-MS column (250 mm x 4.6 mm I.D., 5 microm) was used as stationary phase and the mobile phase consisted of water-acetic acid-acetonitrile (200:1:300) at a flow-rate of 1.0 ml/min. The fluorescence absorbance was monitored at 280 nm for excitation wavelength and 310 nm for emission wavelength. Temperature control was kept at 40 degrees C for the column. The limit of quantitation achieved was 10 ng/ml, and the standard curve was found to be linear in the concentration range of 10-10,000 ng/ml. Under these analytical conditions, a sufficient mephenoxalone plasma concentration profile could be obtained for pharmacokinetic study.