Ceftazidime-avibactam (CAZ-AVI) pharmacokinetics in critically ill patients undergoing continuous venovenous hemodiafiltration (CVVHDF).

Purpose: To investigate the pharmacokinetics (PK) of ceftazidime-avibactam (CAZ-AVI) in critically ill patients undergoing continuous venovenous hemodiafiltration (CVVHDF), and compare with a general phase III trial population.

Methods: A prospective PK study was conducted in critically ill patients who received CVVHDF for acute kidney injury, treated with CAZ-AVI (1000/250 mg or 2000/500 mg q8h). Plasma and CVVHDF-circuit samples were collected to determine CAZ-AVI concentrations.

Formulation-dependent differences in paclitaxel distribution to anatomical sites relevant to chemotherapy-induced peripheral neuropathy.

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting adverse event observed in patients receiving paclitaxel, associated with initial pathological changes in the peripheral nervous system, i.e., distal nerves and dorsal root ganglia (DRG).

Regional distribution of unbound eletriptan and sumatriptan in the CNS and PNS in rats: implications for a potential central action.

Background: Triptans are potent 5-HT receptor agonists used in migraine therapy, thought to act through peripheral mechanisms. It remains unclear whether triptans cross the blood-brain barrier (BBB) sufficiently to stimulate central 5-HT receptors. This study investigates the disposition of eletriptan and sumatriptan in central nervous system (CNS) and peripheral nervous system (PNS) regions and predicts regional 5-HT receptor occupancies at clinically relevant concentrations.

Active CNS delivery of oxycodone in healthy and endotoxemic pigs.

Background: The primary objective of this study was to advance our understanding of active drug uptake at brain barriers in higher species than rodents, by examining oxycodone brain concentrations in pigs.

Methods: This was investigated by a microdialysis study in healthy and endotoxemic conditions to increase the understanding of inter-species translation of putative proton-coupled organic cation (H/OC) antiporter-mediated central nervous system (CNS) drug delivery in health and pathology, and facilitate the extrapolation to humans for improved CNS drug treatment in patients. Additionally, we sought to evaluate the efficacy of lumbar cerebrospinal fluid (CSF) exposure readout as a proxy for brain unbound interstitial fluid (ISF) concentrations.