Relative bioavailability and pharmacokinetic study of two trimetazidine modified release formulations in healthy Bangladeshi male volunteers

Trimetazidine (CAS 5011-34-7) is an effective and well-tolerated antianginal drug that possesses protective properties against ischemia-induced heart injury. The relative bioavailability and pharmacokinetic characteristics of two modified release formulations of 35 mg trimetazidine, one as the test product (Metacard MR) and one as the reference product, were compared in healthy Bangladeshi male volunteers. The randomized, two-way crossover study was conducted in 24 healthy male volunteers after administration of a single 35 mg dose of each modified release formulation after 12-h overnight fasting, with a washout period of two weeks. Blood samples were collected at various time intervals following oral administration and analyzed for trimetazidine concentrations using a validated HPLC method. The pharmacokinetic parameters were determined by a non-compartmental method. After administering a single dose of 35 mg of each trimetazidine formulation, the obtained mean (SD) values for the test and reference products were 104.78 (29.3) and 98.57 (28.7) ng/ml for Cmax; 4.00 (1.1) and 3.54 (1.32) h for t(max); 423.81 (173.9) and 410.01 (195.87) ng x h/ml for AUC0-12; and 472.51 (195.2) and 462.78 (225.13) ng x h/ml for AUC0-infinity respectively. The mean t1/2 was found 3.69 (1.1) h and 3.45 (0.72) h for test and reference products respectively. From paired t-test, no significant differences were observed (p > 0.05) for any pharmacokinetic parameters. The 90% confidence intervals of the test/reference mean ratios of the In-transformed AUC0-12, AUC0-infinity, and Cmax mean values were 106.19% (97.16%-116.06%), 104.74% (95.04%-115.42%) and 106.30% (95.23%-118.66%), respectively. The two formulations demonstrated similar bioavailability with respect to both the rate and extent of trimetazidine absorption.     

Disparities in Mortality Patterns Among Canadian Immigrants and Refugees, 1980–1998: Results of a National Cohort Study

This study examines mortality patterns among Canadian immigrants, including both refugees and non-refugees, 1980–1998. Records of a stratified random sample of Canadian immigrants landing between 1980–1990 (N = 369,936) were probabilistically linked to mortality data (1980–1998). Mortality rates among immigrants were compared to those of the general Canadian population, stratifying by age, sex, immigration category, region of birth and time in Canada. Multivariate analysis examined mortality risks for various immigrant subgroups. Although immigrants presented lower all-cause mortality than the general Canadian population (SMR between 0.34 and 0.58), some cause-specific mortality rates were elevated among immigrants, including mortality from stroke, diabetes, infectious diseases (AIDS and hepatitis among certain subgroups), and certain cancers (liver and nasopharynx). Mortality rates differed by region of birth, and were higher among refugees than other immigrants. These results support the need to consider the heterogeneity of immigrant populations and vulnerable subgroups when developing targeted interventions.