Purpose This study aimed at evaluating bioequivalence of ezetimibe/rosuvastatin fixed dose combination compared to the concomitant administration of individual formulations (ezetimibe and rosuvastatin) in Chinese healthy subjects under fasting conditions. Methods A phase I, randomized, open-label, 2-treatment, 2-period, 2-sequence, crossover study was conducted in healthy Chinese participants under fasting condition. Cmax, AUC0-t and AUC0-∞ from test and individual reference formulations were evaluated to assess bioequivalence. The safety assessments included adverse events (AEs)/treatment-emergent adverse events (TEAEs), potential clinically significant abnormalities (PCSAs) in vital signs, 12-lead electrocardiogram (12-ECG), and clinical laboratory parameters. Findings 68 subjects were enrolled, and 67 were treated. Systemic exposure to rosuvastatin based on Cmax, AUC0-t and AUC0-∞ were similar in both treatments, with respective arithmetic values 12.4 ng/ml, 117 ng·h/mL and 120 ng·h/mL for test formulation and 12.7 ng/ml, 120 ng·h/mL and 123 ng·h/mL for reference formulations. Similarly, systemic exposure to unconjugated ezetimibe were 4.14 ng/ml, 89.7 ng·h/mL and 102 ng·h/mL for test formulation and 3.80 ng/ml, 89.7 ng·h/mL and 102 ng·h/mL for reference formulations. Systemic exposure to total ezetimibe were 70.5 ng/ml, 664 ng·h/mL and 718 ng·h/mL for test formulation and 60.2 ng/ml, 648 ng·h/mL and 702 ng·h/mL for reference formulations. The point estimate for rosuvastatin, unconjugated ezetimibe and total ezetimibe were in the acceptable range of 0.80-1.25. No deaths, serious adverse events (SAE) were reported. Conclusions Fixed dose combination of ezetimibe/rosuvastatin (10mg/10mg) achieved bioequivalence with reference to commercial tablets.

Purpose Exposure of hydrochlorothiazide (HCTZ) has been linked to the increase of skin cancer in the Caucasian population, especially for the squamous cell carcinoma (SCC) but not for basal cell carcinoma (BCC). This study aimed to evaluate the risks of skin cancer between patients receiving HCTZ and those receiving other antihypertensives. Methods This retrospective cohort study was derived from the National Health Insurance Database in Taiwan. We enrolled patients aged 20 years and older who newly receiving antihypertensive medications between 2004 - 2015. We calculated the medication possession ratio (MPR) of the first two years of treatment for patient enrollment and treatment classification, in which patients with MPR above 80% were enrolled and patients were subsequently categorized into receiving HCTZ, other thiazide diuretics, non-thiazide diuretics, and non-diuretic antihypertensives. The Cox proportional hazards model was used to evaluate the risk of skin cancer, and further divided into SCC, and BCC. Results Our study enrolled 41,086, 27,402, 19,613, and 856,782 patients receiving HCTZ, other thiazide diuretics, non-thiazide diuretics, and non-diuretic antihypertensives, respectively. We found BCC risks were similar when comparing HCTZ with other thiazides (adjusted hazard ratio, 0.84; 95% CI: 0.54-1.33), non-thiazide diuretics (0.93; 0.51-1.67), and non-diuretic antihypertensives (0.91; 0.66-1.26). Higher SCC risk was observed in the HCTZ group, compared to other thiazide (1.24; 0.74-2.08), non-thiazide diuretics (1.32; 0.70- 2.51), and non-diuretic antihypertensives (1.23; 0.87-1.73), although the differences were not statistically significant. Conclusions We conclude that skin cancer need not be of major concern to physicians when prescribing antihypertensives for an Asian population.