FDA Approval Summary: Nalmefene Nasal Spray for the Emergency Treatment of Known or Suspected Opioid Overdose.

On May 22, 2023, the United States Food and Drug Administration approved the first nalmefene hydrochloride nasal spray for the emergency treatment of known or suspected opioid overdose in adults and pediatric patients 12 years of age and older. This approval of a new prescription nalmefene hydrochloride nasal spray adds to the available opioid reversal options for hospitals, communities, harm reduction groups, and emergency responders. Due to the life-threatening nature of opioid overdose, conducting randomized, well-controlled clinical efficacy trials in the target patient population is neither ethical nor feasible.

Clinical Pharmacology in Drug Development for Rare Diseases in Neurology: Contributions and Opportunities.

Several challenges are associated with rare disease drug development in neurology. In this article, we summarize the US Food and Drug Administration's experience with clinical drug development for rare neurological diseases and discuss clinical pharmacology's critical contributions to drug development for rare diseases. We used publicly available information to identify and screen drug products approved for rare neurological indications between 1983 and 2019.

Skin and soft tissue concentrations of tedizolid (formerly torezolid), a novel oxazolidinone, following a single oral dose in healthy volunteers.

Plasma concentrations of antimicrobial drugs have long been used to correlate exposure with effect, yet one cannot always assume that unbound plasma and tissue concentrations are similar. Knowledge about unbound tissue concentrations is important in the development of antimicrobial drugs, since most infections are localised in tissues. Therefore, a clinical microdialysis study was conducted to evaluate the distribution of tedizolid (TR-700), the active moiety of the antimicrobial prodrug tedizolid phosphate (TR-701), into interstitial fluid (ISF) of subcutaneous adipose and skeletal muscle tissues following a single oral 600 mg dose of tedizolid phosphate in fasting conditions.

Suppression of ciprofloxacin-induced resistant Pseudomonas aeruginosa in a dynamic kill curve system.

Current dosing approaches for treating microbial infections ignore resistant subpopulations. A clinical isolate of Pseudomonas aeruginosa was cultured in a dynamic in vitro kill curve system designed to simulate the half-lives of drugs in order to evaluate the drug-microbial response relationship. The first dose of ciprofloxacin (CIP) uses a concentration equivalent to the unbound fraction of a 200mg clinical dose.

Pharmacometrics in dose finding or dose optimization of anti-retroviral and anti-tubercular drugs.

Drug development continues to be time consuming, expensive and less efficient, while drug therapy is often administered at suboptimal levels. This is particularly true with anti-infectives for HIV and tuberculosis. The application of pharmacometric principles and models to drug development and pharmacotherapy will improve the drug approval process and selection of optimal dosage regimens or therapeutic combinations.

Preadolescent tobacco smoke exposure leads to acute nicotine dependence but does not affect the rewarding effects of nicotine or nicotine withdrawal in adulthood in rats.

Epidemiological studies indicate that parental smoking increases the risk for smoking in children. However, the underlying mechanisms by which parental smoking increases the risk for smoking are not known. The aim of these studies was to investigate if preadolescent tobacco smoke exposure, postnatal days 21-35, affects the rewarding effects of nicotine and nicotine withdrawal in adult rats.

Tobacco smoke exposure induces nicotine dependence in rats.

Rationale: Tobacco smoke contains nicotine and many other compounds that act in concert on the brain reward system. Therefore, animal models are needed that allow the investigation of chronic exposure to the full spectrum of tobacco smoke constituents.

Objectives: The aim of these studies was to investigate if exposure to tobacco smoke leads to nicotine dependence in rats.

Pharmacokinetic-pharmacodynamic modeling of the in vitro activities of oxazolidinone antimicrobial agents against methicillin-resistant Staphylococcus aureus.

Linezolid is the first FDA-approved oxazolidinone with activity against clinically important gram-positive pathogens, including methicillin (meticillin)-resistant Staphylococcus aureus (MRSA). RWJ-416457 is a new oxazolidinone with an antimicrobial spectrum similar to that of linezolid. The goal of the present study was to develop a general pharmacokinetic (PK)-pharmacodynamic (PD) model that allows the characterization and comparison of the in vitro activities of oxazolidinones, determined in time-kill curve experiments, against MRSA.

Soft-tissue penetration of ceftobiprole in healthy volunteers determined by in vivo microdialysis.

Ceftobiprole is a promising new broad-spectrum cephalosporin with activity against several multidrug-resistant gram-positive and gram-negative species, including methicillin-resistant Staphylococcus aureus. In order to make efficacy predications against these resistant bacteria in soft-tissue infections, i.e.

Cortisol suppression as a surrogate marker for inhaled corticosteroid-induced growth retardation in children.

Exposure of inhaled corticosteroids (ICSs) in pediatrics results in adrenal suppression and growth inhibition. The objective of this study was to assess the relationship of ICS mediated growth retardation with cortisol suppression in asthmatic children. A meta-analysis approach was performed with 33 published articles.

Assessment of the impact of dosing time on the pharmacokinetics/pharmacodynamics of prednisolone.

Prednisolone is widely used for the treatment of inflammation and auto-immune diseases. It exhibits nonlinear pharmacokinetics (PK); and its induced systemic effects (pharmacodynamics (PD)) are commonly evaluated with two biomarkers, cortisol and blood lymphocytes in plasma. Circadian patterns are observed in both biomarkers.

Clinical pharmacokinetics of the diastereomers of arteether in healthy volunteers.

Objective: To evaluate the pharmacokinetics of alpha- and beta-diastereomers of arteether in healthy male volunteers.

Participants And Methods: The study was a single-centre clinical pharmacokinetic trial in healthy male subjects. A group comprising 13 subjects aged 25-50 years received a single intramuscular 150 mg individual dose of the arteether formulation containing alpha- and beta-isomers in a 30:70 ratio.