Atorvastatin (ATS) is the gold-standard treatment worldwide for the management of hypercholesterolemia and prevention of cardiovascular diseases associated with dyslipidemia. Physiologically based pharmacokinetic (PBPK) models have been positioned as a valuable tool for the characterization of complex pharmacokinetic (PK) processes and its extrapolation in special sub-groups of the population, leading to regulatory recognition. Several PBPK models of ATS have been published in the recent years, addressing different aspects of the PK properties of ATS. Therefore, the aims of this review are (i) to summarize the physicochemical and pharmacokinetic characteristics involved in the time-course of ATS, and (ii) to evaluate the major highlights and limitations of the PBPK models of ATS published so far. The PBPK models incorporate common elements related to the physicochemical aspects of ATS. However, there are important differences in relation to the analyte evaluated, the type and effect of transporters and metabolic enzymes, and the permeability value used. Additionally, this review identifies major processes (lactonization, P-gp contribution, ATS-Ca solubility, simultaneous management of multiple analytes, and experimental evidence in the target population), which would enhance the PBPK model prediction to serve as a valid tool for ATS dose optimization.

MBQ-167 is a dual inhibitor of the Rho GTPases Rac and Cdc42 that has shown promising results as an anti-cancer therapeutic at the preclinical stage. This drug has been tested in vitro and in vivo in metastatic breast cancer mouse models. The aim of this study is to develop a physiologically based pharmacokinetic/pharmacodynamic (PBPK-PD) model of MBQ-167 to predict tumor growth inhibition following intraperitoneal (IP) administration in mice bearing Triple Negative and HER2+ mammary tumors. PBPK and Simeoni tumor growth inhibition (TGI) models were developed using the Simcyp V19 Animal Simulator. Our developed PBPK framework adequately describes the time course of MBQ-167 in each of the mouse tissues (e.g., lungs, heart, liver, kidneys, spleen, plasma) and tumor, since the predicted results were consistent with the experimental data. The developed PBPK-PD model successfully predicts tumor shrinkage in HER2+ and triple-negative breast tumors after the intraperitoneal administration of 1 and 10 mg/kg body weight (BW) dose level of MBQ-167 three times a week. The findings from this study suggest that MBQ-167 has a higher net effect and potency inhibiting Triple Negative mammary tumor growth compared to HER2+ and that liver metabolism is the major route of elimination of this drug.

Background and Objective: Arterial Stiffness (AS) measured as pulse wave velocity has emerged in recent years as a hypertension mediated organ damage with independent prognostic value for Cardiovascular (CV) diseases that has also been discussed as a potential cause of Hypertension (HTN). The aim of this study is to (1) evaluate how measurement of AS modifies CV risk calculation by SCORE, (2) to measure the predictive value of AS for incident hypertension in normotensive patients, and (3) to analyze the association between control of HTN and presence of AS in sustained HTN. Patients and Methods: A longitudinal, prospective, observational trial under conditions of daily pharmaceutical and clinical practice will be conducted in approximately 60 community pharmacies of the Iberian Peninsula in normotensive and/or hypertensive patients entering a pharmacy spontaneously. In the first cross-sectional step, AS will be estimated with a semiautomatic, validated device (Mobil-O-Graph^®, IEM), followed by a 10-item questionnaire. The patients will be referred to Primary Care for stratifying risk by SCORE tables and standard evaluation. In the second longitudinal step, patients will be asked to repeat the visit after 12 months. Discussion: This study aims to improve CV risk stratification and to investigate the potential of AS in predicting incident HTN in normotensive subjects. Besides, it will analyze the role of arterial stiffness as an associated factor to prevent control in sustained HTN in a setting of cooperation between community pharmacies and physicians in daily clinical practice.