Impaired liver function: effect on paclitaxel toxicity, dose modifications and overall survival.

Background: The anticancer drug paclitaxel is primarily metabolized in the liver. Previous studies have indicated a correlation between impaired liver function and paclitaxel toxicity, which may indicate dose reduction. Since the evidence is limited, the aim of this study was to investigate the effect of impaired liver function on the hematological toxicity of paclitaxel, dose modifications and overall survival (OS).

Assessing accuracy of ChatGPT in response to questions from day to day pharmaceutical care in hospitals.

Background: The advent of Large Language Models (LLMs) such as ChatGPT introduces opportunities within the medical field. Nonetheless, use of LLM poses a risk when healthcare practitioners and patients present clinical questions to these programs without a comprehensive understanding of its suitability for clinical contexts.

Objective: The objective of this study was to assess ChatGPT's ability to generate appropriate responses to clinical questions that hospital pharmacists could encounter during routine patient care.

Association of Lamotrigine Plasma Concentrations With Efficacy and Toxicity in Patients With Epilepsy: A Retrospective Study.

Background: There is limited evidence to support the currently suggested lamotrigine (LTG) therapeutic reference range of 2.5-15 mg/L for the treatment of seizures. The objective of this study was to evaluate the association of LTG plasma concentrations with the efficacy and toxicity of the treatment in patients with epilepsy.

Performance of ChatGPT on Factual Knowledge Questions Regarding Clinical Pharmacy.

ChatGPT is a language model that was trained on a large dataset including medical literature. Several studies have described the performance of ChatGPT on medical exams. In this study, we examine its performance in answering factual knowledge questions regarding clinical pharmacy.

Poor performance of ChatGPT in clinical rule-guided dose interventions in hospitalized patients with renal dysfunction.

Purpose: Clinical decision support systems (CDSS) are used to identify drugs with potential need for dose modification in patients with renal impairment. ChatGPT holds the potential to be integrated in the electronic health record (EHR) system to give such dosing advices. In this study, we aim to evaluate the performance of ChatGPT in clinical rule-guided dose interventions in hospitalized patients with renal impairment.

Cortisol as Biomarker for CYP17-Inhibition is Associated with Therapy Outcome of Abiraterone Acetate.

Background: Abiraterone acetate is an irreversible 17α-hydroxylase/C17, 20-lyase (CYP17) inhibitor approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC) patients. Inhibition of this enzyme leads to low testosterone and cortisol levels in blood. There is growing evidence that clinical efficacy of abiraterone is related to the rate of suppression of serum testosterone.

Assessment of drug-related problems at the emergency department in older patients living with frailty: pharmacist-led medication reviews within a geriatric care team.

Background: Older patients are vulnerable to experiencing drug related problems (DRPs), which may result in emergency department (ED) visits. However, it is not standard practice to conduct medications reviews during ED visit. The aim of this study was to assess the number of DRPs in older patients living with frailty at the ED, identified through pharmacist-led medication reviews within a geriatric care team, and to determine the acceptance rate of pharmacists' recommendations among hospital physicians and general practitioners or elderly care specialists.

A naïve pooled data approach for extrapolation of Phase 0 microdose trials to therapeutic dosing regimens.

Microdosing is a strategy to obtain knowledge of human pharmacokinetics prior to Phase I clinical trials. The most frequently used method to extrapolate microdose (≤100 μg) pharmacokinetics to therapeutic doses is based on linear extrapolation from a noncompartmental analysis (NCA) with a two-fold acceptance criterion between pharmacokinetic metrics of the extrapolated microdose and the therapeutic dose. The major disadvantage of NCA is the assumption of linear extrapolation of NCA metrics.

Comparison of docetaxel pharmacokinetics between castration-resistant and hormone-sensitive metastatic prostate cancer patients.

Purpose: Recently, docetaxel treatment of metastatic prostate cancer patients shifted towards the hormone-sensitive stage of the disease. There are contradictive reports on differences in toxicity of docetaxel in metastatic hormone-sensitive prostate cancer (mHSPC) and metastatic castration-resistant prostate cancer (mCRPC) patients. Possible differences in toxicity might be attributed to different pharmacokinetics (PK) in the two patient populations.

Dosing Therapeutic Radiopharmaceuticals in Obese Patients.

The prevalence of obesity has increased dramatically in the Western population. Obesity is known to influence not only the proportion of adipose tissue but also physiological processes that could alter drug pharmacokinetics. Yet, there are no specific dosing recommendations for radiopharmaceuticals in this patient population.

Cost-Effectiveness Assessment of Monitoring Abiraterone Levels in Metastatic Castration-Resistant Prostate Cancer Patients.

Objectives: Abiraterone acetate is registered for the treatment of metastatic castration-sensitive and resistant prostate cancer (mCRPC). Treatment outcome is associated with plasma trough concentrations (C) of abiraterone. Patients with a plasma C below the target of 8.

Concomitant intake of abiraterone acetate and food to increase pharmacokinetic exposure: real life data from a therapeutic drug monitoring programme.

Aim: Abiraterone acetate is approved for the treatment of metastatic prostate cancer. At the currently used fixed dose of 1000 mg once daily in modified fasting state, 40% of patients do not reach the efficacy threshold of a minimum plasma concentration (C) ≥ 8.4 ng/mL and are thereby at risk of decreased treatment efficacy.

Exposure-Response Assessment of Enzalutamide and Its Major Metabolites in a Real-World Cohort of Patients with Metastatic Castration-Resistant Prostate Cancer.

Study Objective: Enzalutamide is an oral agent for the treatment of metastatic castration-resistant prostate cancer (mCRPC); N-desmethyl enzalutamide is its active metabolite, which has clinically relevant anti-androgen capacities similar to enzalutamide, and carboxylic acid enzalutamide is an inactive metabolite. The aim of our study was to investigate the relationship between enzalutamide and N-desmethyl enzalutamide exposure and treatment response in a real-world cohort of patients with mCRPC.

Design: Retrospective, observational, pharmacokinetic study.

Bioanalytical LC-MS/MS validation of therapeutic drug monitoring assays in oncology.

Therapeutic drug monitoring (TDM) has shown to benefit patients treated with drugs of many drug classes, among which is oncology. With an increasing demand for drug monitoring, new assays have to be developed and validated. Guidelines for bioanalytical validation issued by the European Medicines Agency and US Food and Drug Administration are applicable for clinical trials and toxicokinetic studies and demand fully validated bioanalytical methods to yield reliable results.

Predictive Value of Microdose Pharmacokinetics.

Phase 0 microdose trials are exploratory studies to early assess human pharmacokinetics of new chemical entities, while limiting drug exposure and risks for participants. The microdose concept is based on the assumption that microdose pharmacokinetics can be extrapolated to pharmacokinetics of a therapeutic dose. However, it is unknown whether microdose pharmacokinetics are actually indicative of the pharmacokinetics at therapeutic dose.

LC-MS/MS assay for the quantification of testosterone, dihydrotestosterone, androstenedione, cortisol and prednisone in plasma from castrated prostate cancer patients treated with abiraterone acetate or enzalutamide.

Prostate cancer is the most common malignancy among men in the Western world. Treatment of this patient population, e.g.

Impact of age on exposure to oral antiandrogen therapies in clinical practice.

Background: Oral antiandrogen therapies are predominantly used in older men, but real-life studies evaluating the impact of age on pharmacokinetic exposure are lacking. This study aims to evaluate the impact of age on the pharmacokinetic profiles of abiraterone acetate and enzalutamide in clinical practice.

Patients And Methods: Retrospective observational study to evaluate the impact of age on the first steady-state sample of patients treated with abiraterone acetate or enzalutamide in routine daily clinical practice.

Therapeutic Drug Monitoring of Oral Anti-Hormonal Drugs in Oncology.

Oral anti-hormonal drugs are essential in the treatment of breast and prostate cancer. It is well known that the interpatient variability in pharmacokinetic exposure is high for these agents and exposure-response relationships exist for many oral anti-hormonal drugs. Yet, they are still administered at fixed doses.

Oral lorazepam can be substituted for intravenous midazolam when weaning paediatric intensive care patients off sedation.

Aim: Intravenous sedatives used in the paediatric intensive care unit (PICU) need to be tapered after prolonged use to prevent iatrogenic withdrawal syndrome (IWS). We evaluated the occurrence of IWS and the levels of sedation before and after conversion from intravenous midazolam to oral lorazepam.

Methods: This was a retrospective, observational, single cohort study of children under the age of 18 admitted to the PICU of the Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands, between January 2013 and December 2014.

An LC-MS/MS method for quantification of the active abiraterone metabolite Δ(4)-abiraterone (D4A) in human plasma.

Δ(4)-Abiraterone (D4A) is a recently discovered active metabolite of the oral anti-androgen drug abiraterone acetate. For quantification of this metabolite in human plasma, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated. Human plasma samples of patients treated with abiraterone acetate were prepared by protein precipitation with acetonitrile.

Development and Validation of an LC-MS/MS Method for the Simultaneous Quantification of Abiraterone, Enzalutamide, and Their Major Metabolites in Human Plasma.

Background: Abiraterone acetate and enzalutamide are 2 novel drugs for the treatment of metastatic castration-resistant prostate cancer. The metabolism of these drugs is extensive. Major metabolites are N-desmethyl enzalutamide, enzalutamide carboxylic acid, abiraterone N-oxide sulfate, and abiraterone sulfate; of which N-desmethyl enzalutamide is reported to possess antiandrogen capacities.

The pathology of alcohol hangover.

Research on human subjects analyzing blood and urine samples determined biological correlates that may explain the pathology of alcohol hangover. These analyses showed that concentrations of various hormones, electrolytes, free fatty acids, triglycerides, lactate, ketone bodies, cortisol, and glucose were not significantly correlated with reported alcohol hangover severity. Also, markers of dehydration (e.