Pharmacokinetic bioequivalence and safety assessment of two metformin hydrochloride tablet formulations using a phase I, randomized, open, two-period, two cross-over, single-dose, fed study in healthy Chinese adult subjects.

OBJECTIVES: To assess the bioequivalence and safety of generic metformin hydrochloride (test preparation) and glucophage (reference preparation) in healthy Chinese subjects. MATERIALS AND METHODS: A bioequivalence and safety assessment of two formulations of metformin (850 mg) using a randomized, open, two-period, two cross-over, single-dose, fed trial in 36 healthy Chinese adult subjects was performed at our center from March 22, 2018, to April 9, 2018. Bioequivalence was determined as two-sided 90% confidence intervals (CI) of the test-to-reference ratio of area under the curve (AUC) and peak concentration (Cmax) for each constituent within 80.00 - 125.00%. SAS 9.4 software was employed for the statistical analysis. RESULTS: One subject was excluded from the trial. The 90% CIs (95.36 - 101.43% for AUC0→t, 95.65 - 101.66% for AUC0→∞; 94.43 - 101.74% for Cmax) of test/reference preparation for these pharmacokinetic parameters were within the range of 80.00 - 125.00%. No severe adverse events were observed during this trial. The two preparations were safe and well-tolerated. CONCLUSION: It was concluded that generic metformin was bioequivalent and as safe as glucophage under fed conditions in healthy Chinese subjects.

Lifestyle Cardiovascular Risk Score, Genetic Risk Score, and Myocardial Infarction in Hispanic/Latino Adults Living in Costa Rica.

BACKGROUND: A lifestyle cardiovascular risk score (LCRS) and a genetic risk score (GRS) have been independently associated with myocardial infarction (MI) in Hispanics/Latinos. Interaction or joint association between these scores has not been examined. Thus, our aim was to assess interactive and joint associations between LCRS and GRS, and each individual lifestyle risk factor, on likelihood of MI. METHODS AND RESULTS: Data included 1534 Costa Rican adults with nonfatal acute MI and 1534 matched controls. The LCRS used estimated coefficients as weights for each factor: unhealthy diet, physical inactivity, smoking, elevated waist:hip ratio, low/high alcohol intake, low socioeconomic status. The GRS included 14 MI-associated risk alleles. Conditional logistic regressions were used to calculate adjusted odds ratios. The odds ratios for MI were 2.72 (2.33, 3.17) per LCRS unit and 1.13 (95% CI 1.06, 1.21) per GRS unit. A significant joint association for highest GRS tertile and highest LCRS tertile and odds of MI was detected (odds ratio=5.43 [3.71, 7.94]; P<1.00×10-7), compared to both lowest tertiles. The odds ratios were 1.74 (1.22, 2.49) under optimal lifestyle and unfavorable genetic profile, and 5.02 (3.46, 7.29) under unhealthy lifestyle but advantageous genetic profile. Significant joint associations were observed for the highest GRS tertile and the highest of each lifestyle component risk category. The interaction term was nonsignificant (P=0.33). CONCLUSIONS: Lifestyle risk factors and genetics are jointly associated with higher odds of MI among Hispanics/Latinos. Individual and combined lifestyle risk factors showed stronger associations. Efforts to improve lifestyle behaviors could help prevent MI regardless of genetic susceptibility.

[Particle Size Distribution, Seasonal Variation Characteristics and Human Exposure Assessment of Heavy Metals in Typical Settled Dust from Beijing].

Four types of dust from dormitories, offices, hotels and roads in Beijing were collected and fractionated into 9 fractions, respectively. Totally 36 samples were obtained and analyzed for heavy metals including Cu, Zn, Cr, Pb, Cd and Ni. Particle size distributions of those heavy metals in these four types of dust were investigated and the influencing mechanisms were discussed. Distribution patterns of the same heavy metal in different types of dust showed various characteristics. Also different metals in the same type of dust represented different distribution patterns. Heavy metals in road dust tended to concentrate in finer particles. Two offices from the same building, located in Beijing, China, were selected to study the seasonality of heavy metals in dust. Dust sampling from Office A was conducted at weekly intervals between March 2012 and August 2012, while dust from Office B was sampled fortnightly from March 2012 to December 2012. Generally, levels of all heavy metals remained stable among different seasons, however, Cr and Pb represented more significant fluctuations than other four heavy metals. Based on the geo-accumulation index method, the pollution of Zn, Cu and Pb was more serious in the investigated samples, and dust from offices and hotels were moderately polluted by Zn. According to the risk assessment results, the carcinogenic health risks of the six heavy metals in the four types of dust were negligible.

Variants in glucose- and circadian rhythm-related genes affect the response of energy expenditure to weight-loss diets: the POUNDS LOST Trial.

BACKGROUND: Circadian rhythm has been shown to be related to glucose metabolism and risk of diabetes, probably through effects on energy balance. Recent genome-wide association studies identified variants in circadian rhythm-related genes (CRY2 and MTNR1B) associated with glucose homeostasis. OBJECTIVE: We tested whether CRY2 and MTNR1B genotypes affected changes in measures of energy expenditure in response to a weight-loss diet intervention in a 2-y randomized clinical trial, the POUNDS (Preventing Overweight Using Novel Dietary Strategies) LOST Trial. DESIGN: The variants CRY2 rs11605924 (n = 721) and MTNR1B rs10830963 (n = 722) were genotyped in overweight or obese adults who were randomly assigned to 1 of 4 weight-loss diets that differed in their proportions of macronutrients. Respiratory quotient (RQ) and resting metabolic rate (RMR) were measured. RESULTS: By 2 y of diet intervention, the A allele of CRY2 rs11605924 was significantly associated with a greater reduction in RQ (P = 0.03) and a greater increase in RMR and RMR/kg (both P = 0.04). The G allele of MTNR1B rs10830963 was significantly associated with a greater increase in RQ (P = 0.01) but was not related to changes in RMR and RMR/kg. In addition, we found significant gene-diet fat interactions for both CRY2 (P-interaction = 0.02) and MTNR1B (P-interaction < 0.001) in relation to 2-y changes in RQ. CONCLUSIONS: Our data indicate that variants in the circadian-related genes CRY2 and MTNR1B may affect long-term changes in energy expenditure, and dietary fat intake may modify the genetic effects. This trial was registered at www.clinicaltrials.gov as NCT00072995.