A Population Pharmacokinetic Model and Dosing Algorithm to Guide the Tacrolimus Starting and Follow-Up Dose in Living and Deceased Donor Kidney Transplant Recipients.

Introduction: Tacrolimus treatment is complicated by its narrow therapeutic range and large inter- and intra-patient variability. This study aimed to develop a population pharmacokinetic model and dosing algorithm to predict an individual's dose requirement following living and deceased donor kidney transplantation.

Methods: In this international, multicenter, retrospective study, data was collected from patients who had received a living or a deceased donor kidney and received tacrolimus twice daily.

A Clinical Pharmacological Perspective on Intraperitoneal Chemotherapy.

Peritoneal metastases (PM), frequently observed in malignancies such as ovarian, colorectal, pancreatic, and gastric cancers, present a significant therapeutic challenge due to poor prognosis and limited effectiveness to systemic chemotherapy. The peritoneal-plasma barrier reduces effective drug transfer from plasma to the peritoneal cavity, reducing cytotoxic effects on PM. Intraperitoneal (IP) chemotherapy offers a locoregional approach, enabling high local drug concentrations that can enhance therapeutic efficacy while limiting systemic toxicity.

Inadequate imipenem dosing in patients with decreased kidney function: a global clinical pharmacokinetic study.

Objectives: A number of population pharmacokinetic (popPK) models of imipenem in critically ill patients are available for dosing optimization, but they represent only a narrow range of kidney functions. This study evaluates the target attainment of on-label regimens through popPK modelling and simulation in patients across different kidney functions.

Methods: A popPK model was built based on two datasets from Switzerland (model development population, 151 patients, 322 concentrations) and externally validated on two datasets from the Czech Republic (19 patients, 111 concentrations) and Vietnam (43 patients, 85 concentrations).

Drug release from docetaxel-entrapped core-crosslinked polymeric micelles: A population pharmacokinetic modelling approach based on clinical data.

CPC634 is a core-crosslinked polymeric micelle entrapping docetaxel (DTX) developed to improve tolerability and tumour drug accumulation compared to conventional DTX. A pH-responsive covalent sulfone ester linker allows for controlled native DTX release. Prior research has shown CPC634's dose-proportional clinical pharmacokinetics (PK) and enhanced tumour uptake.

If it does not help, it might hurt: Pharmacodynamics of a second IVIg course in Guillain-Barré syndrome.

Objectives: Intravenous immunoglobulin (IVIg) is an effective treatment for Guillain-Barré syndrome (GBS), but recovery varies between patients. This study aims to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of a single and a second IVIg dose (SID) in patients with GBS.

Methods: Data were analyzed from the SID-GBS trial, a double-blind, randomized, placebo-controlled study.

Pharmacokinetics of betamethasone in pre-eclampsia: An in vivo and ex vivo study.

Aims: To enhance understanding of betamethasone and its metabolites' pharmacokinetics in pregnancy, specifically early-onset pre-eclampsia, through a population pharmacokinetic model. Additionally, to investigate the placental metabolism and transfer of betamethasone and its main metabolites.

Methods: A prospective, single-centre pharmacokinetic study was conducted in pregnant women (n = 28) with imminent preterm birth treated with intramuscular betamethasone.

The synergistic effect of the combination of polymyxin B and rifampicin in a murine neutropenic thigh infection model with E. coli and K. pneumoniae.

Background: Antibiotic combination therapy is increasingly used to treat MDR pathogens. In vitro studies suggest that the polymyxin B/rifampicin combination might be synergistic. Therefore, the pharmacodynamics of rifampicin as monotherapy and combined with polymyxin B were studied in Escherichia coli- and Klebsiella pneumoniae-infected mice.

Variable temocillin protein binding and pharmacokinetics in different clinical conditions: Implications for target attainment.

Aims: The beta-lactam antibiotic temocillin is increasingly used to treat extended-spectrum beta-lactamase (ESBL-producing) strains; however, its protein binding is complex. This study aims to predict unbound temocillin concentrations in various participant groups to determine its impact on the probability of target attainment (PTA) and to improve dosing recommendations.

Methods: The plasma pharmacokinetics were analysed using non-linear mixed-effects modelling.

Pharmacodynamics of NOSO-502 studied in vitro and in vivo: determination of the dominant pharmacodynamic index driver.

Background: NOSO-5O2 is the first clinical candidate of a new antimicrobial class-the odilorhabdins. The pharmacodynamics of NOSO-502 were studied in vitro and in vivo to establish the pharmacodynamic index (PDI) driver.

Methods: A dilutional pharmacokinetic system was used for in vitro experiments.

Selecting the Best Pharmacokinetic Models for a Priori Model-Informed Precision Dosing with Model Ensembling.

Background And Objective: When utilizing population pharmacokinetic (popPK) models for a priori dosage individualization, selecting the best model is crucial to obtain adequate doses. We developed and evaluated several model-selection and ensembling methods, using external evaluation on the basis of therapeutic drug monitoring (TDM) samples to identify the best (set of) models per patient for a priori dosage individualization.

Methods: PK data and models describing both hospitalized patients (n = 134) receiving continuous vancomycin (26 models) and patients (n = 92) receiving imatinib in an outpatient setting (12 models) are included.

Removing the physician from the equation: Patient-controlled, home-based therapeutic drug self-monitoring of tacrolimus.

The dosing of tacrolimus, which forms the backbone of immunosuppressive therapy after kidney transplantation, is complex. This is due to its variable pharmacokinetics (both between and within individual patients), narrow therapeutic index, and the severe consequences of over- and underexposure, which may cause toxicity and rejection, respectively. Tacrolimus is, therefore, routinely dosed by means of therapeutic drug monitoring (TDM).

Intraperitoneal pharmacokinetics of systemic oxaliplatin, 5-fluorouracil and bevacizumab in patients with colorectal peritoneal metastases.

Background: Peritoneal metastases (PM) commonly occur in colorectal cancer patients. Systemic chemotherapy yields poor outcomes for these patients. It is hypothesised that traditional systemic chemotherapy is not very effective for this patient population.

Individualized dosing algorithms for tacrolimus in kidney transplant recipients: current status and unmet needs.

Introduction: Tacrolimus is a potent immunosuppressive drug with many side effects including nephrotoxicity and post-transplant diabetes mellitus. To limit its toxicity, therapeutic drug monitoring (TDM) is performed. However, tacrolimus' pharmacokinetics are highly variable within and between individuals, which complicates their clinical management.

Towards precision dosing of aripiprazole in children and adolescents with autism spectrum disorder: Linking blood levels to weight gain and effectiveness.

Aims: Aripiprazole is one of the most commonly prescribed antipsychotic drugs to children and adolescents worldwide, but it is associated with serious side-effects, including weight gain. This study assessed the population pharmacokinetics of aripiprazole and its active metabolite and investigated the relationship between pharmacokinetic parameters and body mass index (BMI) in children and adolescents with autism spectrum disorder (ASD) and behavioural problems. Secondary outcomes were metabolic, endocrine, extrapyramidal and cardiac side-effects and drug effectiveness.

Toward model-informed precision dosing for tamoxifen: A population-pharmacokinetic model with a continuous CYP2D6 activity scale.

Background: Tamoxifen is important in the adjuvant treatment of breast cancer. A plasma concentration of the active metabolite endoxifen of > 16 nM is associated with a lower risk of breast cancer-recurrence. Since inter-individual variability is high and > 20 % of patients do not reach endoxifen levels > 16 nM with the standard dose tamoxifen, therapeutic drug monitoring is advised.

Population Pharmacokinetic Modelling of Intravenous Immunoglobulin Treatment in Patients with Guillain-Barré Syndrome.

Background And Objective: Intravenous immunoglobulin (IVIg) at a standard dosage is the treatment of choice for Guillain-Barré syndrome. The pharmacokinetics, however, is highly variable between patients, and a rapid clearance of IVIg is associated with poor recovery. We aimed to develop a model to predict the pharmacokinetics of a standard 5-day IVIg course (0.

Pharmacokinetics of Haloperidol in Critically Ill Patients: Is There an Association with Inflammation?

Haloperidol is considered the first-line treatment for delirium in critically ill patients. However, clinical evidence of efficacy is lacking and no pharmacokinetic studies have been performed in intensive care unit (ICU) patients. The aim of this study was to establish a pharmacokinetic model to describe the PK in this population to improve insight into dosing.

Population Pharmacokinetics of Oxycodone and Metabolites in Patients with Cancer-Related Pain.

Oxycodone is frequently used for treating cancer-related pain, while not much is known about the factors that influence treatment outcomes in these patients. We aim to unravel these factors by developing a population-pharmacokinetic model to assess the pharmacokinetics of oxycodone and its metabolites in cancer patients, and to associate this with pain scores, and adverse events. Hospitalized patients with cancer-related pain, who were treated with oral oxycodone, could participate.

Prospective real-world study on the pharmacokinetics of pembrolizumab in patients with solid tumors.

Background: Dosing schemes of pembrolizumab (anti-programmed cell death protein 1 monoclonal antibody) are solely based on pharmacokinetic (PK) modelling derived from phase I-III trials. The current study aimed to determine factors affecting PK and its relationship with clinical outcome in the real-world setting.

Methods: Advanced-stage cancer patients, who were treated with pembrolizumab monotherapy (2 mg/kg Q3W or 200 mg flat Q3W), were prospectively included for serial sampling to obtain trough concentrations.