Therapeutic drug monitoring

PURPOSE: Infectious disease pharmacists and physicians overseeing antimicrobial stewardship programs possess expertise and often advanced certification in management of antiretrovirals to treat HIV. Stewardship programs are responsible for managing facility formularies and must stay up to date with the latest antiretrovirals, including once daily formulations and depot injectables. Furthermore, stewardship program members need to understand drug-interactions, short-, and long-term toxicities of these regimens, including dyslipidemia and cardiovascular effects...

We present a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying fenfluramine (FFA), its active metabolite norfenfluramine (norFFA), and Epidyolex®, a pure cannabidiol (CBD) oral solution in plasma. Recently approved by the EMA for the adjunctive treatment of refractory seizures in patients with Dravet and Lennox-Gastaut syndromes aged above 2 years, FFA and CBD still do not have established therapeutic blood ranges, and thus need careful drug monitoring to manage potential pharmacokinetic and pharmacodynamic interactions...

Parkinson's disease (PD) is a complex neurodegenerative disorder characterized not only by its hallmark motor symptoms but also by a myriad of non-motor manifestations, including cognitive decline, autonomic manifestations, and gastrointestinal disturbances. Amidst these, a lesser-known but critical aspect is the increased risk of functional deficiency of pyridoxine (vitamin B6 ) in patients with PD, which is linked to an increased risk of seizures. This review investigates the intersection of PD, new-onset seizures, and pyridoxine deficiency, aiming to elucidate the significance of these associations and their contributions to the neurologic burden in PD...

In Spain, 33% of adults aged 30 to 79 years (10 million) were hypertensive in 2019. Among them, 68% were diagnosed, 57% received drug therapy, and effective therapeutic coverage (control) reached 33%. Both diagnosis and control show geographical and social disparities. Approximately 46 000 cardiovascular deaths per year are attributable to hypertension. In recent decades, the control of hypertension has increased, due to improvements in lifestyle measures and increased use of polytherapy, coinciding with a reduction in stroke mortality...

BACKGROUND: Delamanid (DLM) is a relatively new drug for drug-resistant tuberculosis (DR-TB) that has been used in Indonesia since 2019 despite its limited safety data. DLM is known to inhibit hERG potassium channel with the potential to cause QT prolongation which eventually leads to Torsades de pointes (TdP). OBJECTIVE: This study aims to analyse the changes of QTc interval in DR-TB patients on DLM regimen compared to shorter treatment regimens (STR). METHODS: A retrospective cohort was implemented on secondary data obtained from two participating hospitals...

MET exon 14 skipping alterations and MET amplifications are recognized as oncogenic and targetable genetic changes in cancer patients. The treatment of MET-selective tyrosine kinase inhibitors (TKIs) in this specific population has shown encouraging therapeutic results. However, a comprehensive understanding of the potential toxicities linked to these agents is still lacking. The present pharmacovigilance analysis was carried out using the FDA Adverse Event Reporting System database to assess notable adverse events associated with MET-selective TKIs...

OBJECTIVES: Interferon (IFN)-induced lung injury is a rare but severe complication. Studies are needed to elucidate the demographic characteristics, clinical manifestations, and prognostic features of IFN-induced interstitial lung disease (ILD). CASE REPORT: We report a patient with chronic hepatitis who developed ILD after interferon monotherapy. To further clarify the clinical characteristics of such patients, we searched for cases in which lung injury was documented as a side effect of hepatitis treatment and systematically analyzed all case reports for clinical manifestations, type of treatment, and outcomes...

Acute myeloid leukaemia (AML) is characterized by uncontrolled proliferation of myeloid progenitor cells and impaired maturation, leading to immature cell accumulation in the bone marrow and bloodstream, resulting in hematopoietic dysfunction. Chemoresistance, hyperactivity of survival pathways, and miRNA alteration are major factors contributing to treatment failure and poor outcomes in AML patients. This study aimed to investigate the impact of the pharmacological p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 on the chemoresistance potential of AML stem cell line KG1a to the therapeutic drug daunorubicin (DNR)...

The personalised oncology paradigm remains challenging to deliver despite technological advances in genomics-based identification of actionable variants combined with the increasing focus of drug development on these specific targets. To ensure we continue to build concerted momentum to improve outcomes across all cancer types, financial, technological and operational barriers need to be addressed. For example, complete integration and certification of the 'molecular tumour board' into 'standard of care' ensures a unified clinical decision pathway that both counteracts fragmentation and is the cornerstone of evidence-based delivery inside and outside of a research setting...

Over the last decade, the therapeutic landscape for hematological malignancies (HMs) has witnessed a remarkable surge in the development of novel biological and small-molecule-targeted immunomodulatory agents. These therapies have drastically improved survival, but some come at the cost of increased risk of bacterial, viral, and/or fungal infections and on-target off-tumor immunological side effects. To mitigate such risks, physicians must be well informed about infectious complications and necessary preventive measures, such as screening, vaccinations, and antimicrobial prophylaxis...

As the world grapples with the relentless challenges posed by diseases like malaria, the advent of sophisticated computational tools has emerged as a beacon of hope in the quest for effective treatments. In this study we delve into the strategies behind computational tools encompassing virtual screening, molecular docking, artificial intelligence (AI), and machine learning (ML). We assess their effectiveness and contribution to the progress of malaria treatment. The convergence of these computational strategies, coupled with the ever-increasing power of computing systems, has ushered in a new era of drug discovery, holding immense promise for the eradication of malaria...

Steatotic liver disease (SLD) displays a dynamic and complex disease phenotype. Consequently, the metabolic dysfunction-associated steatotic liver disease (MASLD)/metabolic dysfunction-associated steatohepatitis (MASH) therapeutic pipeline is expanding rapidly and in multiple directions. In parallel, noninvasive tools for diagnosing and monitoring responses to therapeutic interventions are being studied, and clinically feasible findings are being explored as primary outcomes in interventional trials. The realization that distinct subgroups exist under the umbrella of SLD should guide more precise and personalized treatment recommendations and facilitate advancements in pharmacotherapeutics...

BACKGROUND: Limited epidemiologic studies have been conducted in Jordan describing the HIV epidemic. This study aimed to address this gap to inform HIV prevention and control. METHODS: A nationally-representative cross-sectional study was conducted among adults living with HIV in Jordan. Laboratory testing included HIV viral load and next-generation-sequencing-based clinical genotype. Log-binomial regression estimated risk ratios (RRs) and 95% confidence intervals (CIs)...

BACKGROUND: The cardiotoxic effects of anthracyclines therapy are well recognized, both in the short and long term. Echocardiography allows monitoring of cancer patients treated with this class of drugs by serial assessment of left ventricle ejection fraction (LVEF) as a surrogate of systolic function. However, changes in myocardial function may occur late in the process when cardiac damage is already established. Novel cardiac magnetic resonance (CMR) parametric techniques, like native T1 mapping and extra-cellular volume (ECV), may detect subclinical myocardial damage in these patients, recognizing early signs of cardiotoxicity before development of overt cancer therapy-related cardiac dysfunction (CTRCD) and prompting tailored therapeutic and follow-up strategies to improve outcome...

INTRODUCTION: The role of upadacitinib in the management of moderate to severe atopic dermatitis seems promising, but more data on its efficacy and safety are needed. This study endeavors to assess the practical impact and safety of upadacitinib in patients with moderate to severe atopic dermatitis. The study aims to evaluate the efficacy and safety of upadacitinib in the treatment of moderate to severe atopic dermatitis, focusing on analyzing patient responses to the treatment. METHODS: In this study, adult patients diagnosed with moderate to severe atopic dermatitis received upadacitinib at daily doses of 15 mg or 30 mg, as prescribed by their attending physicians...

CONTEXT: Cabozantinib combined with immune checkpoint inhibitors (ICIs) has brought a new therapeutic effect for the medical treatment of renal cell carcinoma (RCC). OBJECTIVES: We performed a meta-analysis of randomized controlled trials and single-arm trials to evaluate the efficacy and safety of cabozantinib plus ICIs in RCC. METHODS: We extracted data from PubMed, Cochrane, Medline and Embase databases, and rated literature quality through Cochrane risk of bias tool and MINORS...

Creatine transporter deficiency (CTD) is an X-linked disease caused by mutations in the Slc6a8 gene. The impaired creatine uptake in the brain leads to developmental delays with intellectual disability. We hypothesized that deficient creatine uptake in CTD cerebral cells impact methylation balance leading to alterations of genes and proteins expression by epigenetic mechanism. In this study, we determined the status of nucleic acid methylation in both Slc6a8 knockout mouse model and brain organoids derived from CTD patients' cells...

BACKGROUND: Executing structured medication reviews (SMRs) in primary care to optimize drug treatment is considered standard care of community pharmacists in the Netherlands. Patients with Parkinson's disease (PD) often face complex drug regimens for their symptomatic treatment and might, therefore, benefit from an SMR. However, previously, no effect of an SMR on quality of life in PD was found. In trying to improve the case management of PD, it is interesting to understand if and to what extent SMRs in PD patients are of added value in the pharmacist's opinion and what are assumed facilitating and hindering factors...

The authors reviewed the literature, published between 2018 and 2023, on treating bipolar disorder in the perinatal period in order to summarize current treatment perspectives. Mood episodes occur during pregnancy and there are high rates of both initial onset and recurrence in the postpartum period. Bipolar disorder itself is associated with higher risks of adverse pregnancy outcomes, including gestational hypertension, hemorrhage, cesarean delivery, and small for gestational age infants. A general principle of perinatal treatment includes maintaining psychiatric stability of the pregnant person while reducing medication exposure risk to the fetus...

5-Fluorouracil is an antimetabolite drug indicated for cancer treatment. Therapeutic drug monitoring of 5-Fluorouracil is necessary because 5-Fluorouracil has narrow therapeutic window and its concentration in blood is affected by individual conditions, like gene polymorphisms. Dried Blood Spot (DBS) is one of the biosampling methods used for therapeutic drug monitoring. Asides from reducing patients' discomfort, the use of DBS can increase 5-Fluorouracil stability by stopping the enzymes activity in blood...