Pharmacokinetics of dexamethasone in tuberculosis meningitis.

Introduction: Dexamethasone is recommended as adjunctive therapy for tuberculosis meningitis (TBM). Co-administration with rifampicin is expected to reduce dexamethasone exposure in TBM, an effect that may be more pronounced with the higher rifampicin doses currently being evaluated in clinical trials.

Methods: This pharmacokinetic study was nested in a randomised controlled trial comparing the safety of high-dose rifampicin (oral, 35 mg/kg; intravenous, 20 mg/kg) plus linezolid, with or without aspirin, vs standard-dose rifampicin (10 mg/kg) for adults with HIV-associated TBM.

Population pharmacokinetics of pyrazinamide and isoniazid in plasma and cerebrospinal fluid from South African adults with tuberculous meningitis.

Pyrazinamide and isoniazid are first-line drugs for tuberculous meningitis (TBM), but limited information is available on their plasma pharmacokinetics, and particularly cerebrospinal fluid (CSF) penetration, in patients with TBM. Any potential effect of co-administration with high-dose rifampicin, also being evaluated in trials for TBM, is unknown. Understanding this is important for dose optimisation.

Population Pharmacokinetics of Rifampicin in Plasma and Cerebrospinal Fluid in Adults With Tuberculosis Meningitis.

Background: Several ongoing clinical trials are evaluating high-dose rifampicin (up to 35 mg/kg) for tuberculous meningitis (TBM). However, rifampicin pharmacokinetics at higher doses is not fully characterized, particularly in cerebrospinal fluid (CSF), the site of TBM disease.

Methods: In a randomized controlled trial, adults with HIV-associated TBM were assigned to experimental arms of high-dose rifampicin (oral, 35 mg/kg; intravenous, 20 mg/kg) plus linezolid, with or without aspirin, or a control arm that received the standard of care with 10 mg/kg of oral rifampicin.

Rifabutin central nervous system concentrations in a rabbit model of tuberculous meningitis.

Tuberculous meningitis (TBM) has a high mortality, possibly due to suboptimal therapy. Drug exposure data of antituberculosis agents in the central nervous system (CNS) are required to develop more effective regimens. Rifabutin is a rifamycin equivalently potent to rifampin in human pulmonary tuberculosis.

Rifampicin and protein concentrations in paired spinal versus ventricular cerebrospinal fluid samples of children with tuberculous meningitis.

Background: Tuberculous meningitis (TBM) is the most lethal form of TB. To study the disease, drug concentrations in samples obtained from the spinal CSF are usually used to reflect brain concentrations. Emerging data suggest that transport of substances across capillaries in the brain (ventricular CSF) and spinal cord may differ.

Linezolid Population Pharmacokinetic Model in Plasma and Cerebrospinal Fluid Among Patients With Tuberculosis Meningitis.

Background: Linezolid is evaluated in novel treatment regimens for tuberculous meningitis (TBM). Linezolid pharmacokinetics have not been characterized in this population, particularly in cerebrospinal fluid (CSF), as well as, following its co-administration with high-dose rifampicin. We aimed to characterize linezolid plasma and CSF pharmacokinetics in adults with TBM.

Pharmacokinetics of antitubercular drugs in patients hospitalized with HIV-associated tuberculosis: a population modeling analysis.

Background: Early mortality among hospitalized HIV-associated tuberculosis (TB/HIV) patients is high despite treatment. The pharmacokinetics of rifampicin, isoniazid, and pyrazinamide were investigated in hospitalized TB/HIV patients and a cohort of outpatients with TB (with or without HIV) to determine whether drug exposures differed between groups.

Methods: Standard first-line TB treatment was given daily as per national guidelines, which consisted of oral 4-drug fixed-dose combination tablets containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol.

Preparation and Optimization of Fast-Disintegrating Tablet Containing Naratriptan Hydrochloride Using D-Optimal Mixture Design.

Optimization of a lyophilized fast-disintegrating tablet (LFDT) formulation containing naratriptan hydrochloride, an antimigraine drug, was the foremost objective of the study, aiming in achieving fast headache pain relief. The Design-Expert® v10 software was used to generate formulations using D-optimal mixture design with four components: gelatin (X), hydrolyzed gelatin (X), glycine (X), and mannitol (X) of total solid material (TSM) w/w. The effect of the relative proportion of each component was determined on friability (Y), hardness (Y), and in vitro disintegration time (Y), which was then applied for formulation optimization.

A Contagious Disorder: Folie à Deux and Dementia.

Background: Folie à deux is a clinical condition that was first described in 19th century. It is a psychotic disorder in which two closely associated individuals share a similar delusional system.

Objectives: The aim of this article is to review the nosological significance of folie à deux and to explore the disorder among patients with dementia.

An Unusual Case of Acute Psychosis With Obsessive-Compulsive Features Following Arsenic Poisoning.

Arsenic exposure, particularly the chronic type, can lead to poisoning with manifestations presenting in multiple organ systems. However, acute psychosis is not a commonly described manifestation of arsenic exposure. In this report, we present the case of a patient who developed acute psychosis with hallucinations, disorganized thinking, and obsessive-compulsive symptoms following chronic occupational arsenic exposure.

Early-Life Trauma in Hospitalized Patients With Mood Disorders and Its Association With Clinical Outcomes.

Background: The prevalence of childhood trauma and its impact on clinical outcomes in hospitalized patients with mood disorders is unknown. We studied the frequency of childhood trauma among inpatient adults with mood disorders and its association with clinical outcomes.

Methods: Patients admitted to our hospital with a primary diagnosis of mood disorders completed the short form of the Early Trauma Inventory-Self-Report (ETISR-SF), the Sheehan Disability Scale, and the Clinician-Rated Dimensions of Psychosis Symptom Severity scale.