Validation and clinical evaluation of an ultra-performance liquid chromatography with ultraviolet detector method for plasma quantification of micafungin.

Background: Factors associated with interindividual variability in the pharmacokinetics of micafungin have been identified. This variability can cause underexposure and loss of drug efficacy. For this reason, a simple, fast, cost-effective and sensitive ultra-performance liquid chromatography ultraviolet detector (UPLC-UV) method was developed and validated for the quantification of micafungin.

Model-Informed Precision Dosing (MIPD).

Model-informed precision dosing (MIPD) is an advanced quantitative approach focusing on individualized dosage optimization, integrating complex mathematical and statistical models of drugs and disease combined with individual demographic and clinical patient characteristics [...

Physiologically-based pharmacokinetic modelling and dosing evaluation of gentamicin in neonates using PhysPK.

Each year, infections caused around the 25% of neonatal deaths. Early empirical treatments help to reduce this mortality, although optimized dosing regimens are still lacking. The aims were to develop and validate a gentamicin physiologically-based pharmacokinetic (PBPK) model and then potentially explore dosing regimens in neonates using pharmacokinetic and pharmacodynamic criteria.

External evaluation of population pharmacokinetic models of imatinib in adults diagnosed with chronic myeloid leukaemia.

Aims: Imatinib is considered the standard first-line treatment in newly diagnosed patients with chronic-phase myeloid leukaemia (CML). Several imatinib population pharmacokinetic (popPK) models have been developed. However, their predictive performance has not been well established when extrapolated to different populations.

Population pharmacokinetics of a posaconazole tablet formulation in transplant adult allogeneic stem cell recipients.

Background: Posaconazole is an antifungal agent extensively used as a prophylaxis for invasive fungal infections (IFIs) in allogeneic stem cell transplant (SCT) recipients. Low posaconazole concentrations have been associated with reduced clinical response. The aim of this study was to develop a population pharmacokinetic (popPK) model of a posaconazole tablet formulation in allogeneic SCT adult recipients for supporting model-informed precision dosing (MIPD).

Evaluation of Current Amikacin Dosing Recommendations and Development of an Interactive Nomogram: The Role of Albumin.

This study aimed to evaluate the potential efficacy and safety of the amikacin dosage proposed by the main guidelines and to develop an interactive nomogram, especially focused on the potential impact of albumin on initial dosage recommendation. The probability of target attainment (PTA) for each of the different dosing recommendations was calculated through stochastic simulations based on pharmacokinetic/pharmacodynamic (PKPD) criteria. Large efficacy and safety differences were observed for the evaluated amikacin dosing guidelines together with a significant impact of albumin concentrations on efficacy and safety.

Biomarkers of disease activity and other factors as predictors of adalimumab pharmacokinetics in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is commonly treated with adalimumab. The main objective of the study was to develop a population pharmacokinetic model of adalimumab in IBD patients evaluating the potential biomarkers of disease activity and other factors and its implications in adalimumab dosing. A prospective observational study was performed in adult patients diagnosed with Crohn's disease and ulcerative colitis treated with adalimumab and following a proactive therapeutic drug monitoring of serum concentrations.

Amikacin initial dosage in patients with hypoalbuminaemia: an interactive tool based on a population pharmacokinetic approach.

Objectives: To characterize amikacin population pharmacokinetics in patients with hypoalbuminaemia and to develop a model-based interactive application for amikacin initial dosage.

Methods: A population pharmacokinetic model was developed using a non-linear mixed-effects modelling approach (NONMEM) with amikacin concentration-time data collected from clinical practice (75% hypoalbuminaemic patients). Goodness-of-fit plots, minimum objective function value, prediction-corrected visual predictive check, bootstrapping, precision and bias of parameter estimates were used for model evaluation.

Population Pharmacokinetics of Apalutamide and its Active Metabolite N-Desmethyl-Apalutamide in Healthy and Castration-Resistant Prostate Cancer Subjects.

Background: Apalutamide is a next-generation androgen receptor inhibitor approved for treatment of subjects with high-risk, non-metastatic, castration-resistant prostate cancer (NM-CRPC).

Objective: The objective of this study was to characterize the population pharmacokinetics of apalutamide and its metabolite N-desmethyl-apalutamide in healthy male and castration-resistant prostate cancer subjects.

Methods: Plasma concentration data for apalutamide and N-desmethyl-apalutamide from 1092 subjects (seven clinical studies) receiving oral apalutamide (30-480 mg) once daily were pooled for a population pharmacokinetic analysis using a non-linear mixed-effect modelling approach.

Evaluation of renal function equations to predict amikacin clearance.

: To evaluate the predictive performance of eight renal function equations to describe amikacin elimination in a large standard population with a wide range of age. : Retrospective study of adult hospitalized patients treated with amikacin and monitored in the clinical pharmacokinetics laboratory of a pharmacy service. Renal function was calculated as Cockcroft-Gault with total, adjusted and ideal body weight, MDRD-4, CKD-EPI, rLM, BIS1, and FAS.

Population pharmacokinetics of doxorubicin and doxorubicinol in patients diagnosed with non-Hodgkin's lymphoma.

Aims: The aims of the study were: (i) to characterize the pharmacokinetics (PK) of doxorubicin (DOX) and doxorubicinol (DOXol) in patients diagnosed with non-Hodgkin's lymphoma (NHL) using a population approach; (ii) to evaluate the influence of various covariates on the PK of DOX; and (iii) to evaluate the role of DOX and DOXol exposure in haematological toxicity.

Methods: Population PK modelling (using NONMEM) was performed using DOX and DOXol plasma concentration-time data from 45 NHL patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone). The influence of drug exposure on haematological toxicity was analysed using the Mann-Whitney-Wilcoxon test.

Usalpharma: a cloud-based architecture to support quality assurance training processes in health area using virtual worlds.

This paper discusses how cloud-based architectures can extend and enhance the functionality of the training environments based on virtual worlds and how, from this cloud perspective, we can provide support to analysis of training processes in the area of health, specifically in the field of training processes in quality assurance for pharmaceutical laboratories, presenting a tool for data retrieval and analysis that allows facing the knowledge discovery in the happenings inside the virtual worlds.

Validation and clinical evaluation of a UHPLC method with fluorescence detector for plasma quantification of doxorubicin and doxorubicinol in haematological patients.

A rapid and simple UHPLC-fluorescence detection method for the quantification of doxorubicin and its main metabolite, doxorubicinol, in human plasma has been developed. The method was also validated for its application in therapeutic drug monitoring, a clinical approach used in the optimization of oncologic treatments. Following a single protein precipitation step, chromatographic separation was achieved using a C18 column (50mm×2.