Blood pressure lowering effect of statin drugs with an application to rosuvastatin

Hyperlipidemia and hypertension are among the major risk factors for cardiovascular disease (CVD) and they often co-exist within a single patient. Recently, many studies published results regarding the potential role of statins in decreasing blood pressure (BP) however there is still a controversy over the efficacy of statin therapy on BP. This study aimed to investigate the potential role of rosuvastatin in BP lowering properties in Korean population. Data were taken from three randomized, multiple-dose cross over studies for rosuvastatin, angiotensin II receptor blocker (ARB) and metformin monotherapies and the combined therapy of rosuvastatin and ARB, in total of 91 healthy male normotensive subjects. Measurements of systolic blood pressure (SBP), diastolic blood pressure (DBP) at the baseline before treatment begins and for 24 hours after the last dose were used in the analysis. The analysis variables used were (i) the mean change in steady-state BP from the baseline, symbolized as ΔBP, and (ii) the difference in ΔBP between the ARB monotherapy and the combined therapy, symbolized as ΔBP,d. The ΔBP and ΔBP,d for SBP from each study varied in -0.1 ~ -1.3 mmHg and 1.2 ~ 1.6 mmHg, respectively, and were not significantly different from zero. The ΔBP and ΔBP,d for DBP from each study varied in -2.8 ~ -1.4 mmHg and -2.9 ~ -1.8, respectively, which were statistically significant for ΔBP (p 0.05). These results indicated that the rosuvastatin monotherapy may produce small blood pressure lowing effect in DBP.

Assessment of statistical power for covariate effects in data from phase I clinical trials

One of the important purposes in population pharmacokinetic studies is to investigate the relationships between parameters and covariates to describe parameter variability. The purpose of this study is to evaluate the model's ability to correctly detect the parameter-covariate relationship that can be observed in phase I clinical trials. Data were simulated from a two-compartment model with zero-order absorption and first-order elimination, which was built from valsartan's concentration data collected from a previously conducted study. With creatinine clearance (CLCR) being used as a covariate to be tested, 3 different significance levels of 0.001