Pharmacokinetics of fluconazole in critically ill patients with acute kidney injury receiving sustained low-efficiency diafiltration.

Fluconazole is a widely used antifungal agent in critically ill patients. It is predominantly (60-80%) excreted unchanged in urine. Sustained low-efficiency diafiltration (SLED-f) is increasingly being utilised in critically ill patients because of its practical advantages over continuous renal replacement therapy.

Simultaneous determination of seven β-lactam antibiotics in human plasma for therapeutic drug monitoring and pharmacokinetic studies.

There is strong evidence in literature supporting the benefit of monitoring plasma concentrations of β-lactam antibiotics in the critically ill to ensure appropriateness of dosing. The objective of this work was to develop a method for the simultaneous determination of total concentrations piperacillin, benzylpenicillin, flucloxacillin, meropenem, ertapenem, cephazolin and ceftazidime in human plasma. Sample preparation involved protein precipitation with acetonitrile containing 0.

Altered pharmacokinetics of piperacillin in febrile neutropenic patients with hematological malignancy.

This study assessed the pharmacokinetics and dosing adequacy of piperacillin in febrile neutropenic patients after the first dose. Pharmacokinetic analysis was performed using noncompartmental methods. We observed an elevated volume of distribution (29.

An international, multicentre survey of β-lactam antibiotic therapeutic drug monitoring practice in intensive care units.

Objectives: Emerging evidence supports the use of therapeutic drug monitoring (TDM) of β-lactams for intensive care unit (ICU) patients to optimize drug exposure, although limited detail is available on how sites run this service in practice. This multicentre survey study was performed to describe the various approaches used for β-lactam TDM in ICUs.

Methods: A questionnaire survey was developed to describe various aspects relating to the conduct of β-lactam TDM in an ICU setting.

Current and emerging pharmacotherapeutic options for smoking cessation.

Tobacco smoking remains the single most preventable cause of morbidity and mortality in developed countries and poses a significant threat across developing countries where tobacco use prevalence is increasing. Nicotine dependence is a chronic disease often requiring multiple attempts to quit; repeated interventions with pharmacotherapeutic aids have become more popular as part of cessation therapies. First-line medications of known efficacy in the general population include varenicline tartrate, bupropion hydrochloride, nicotine replacement therapy products, or a combination thereof.

Fluorescein derivatives in intravital fluorescence imaging.

Intravital fluorescence microscopy enables the direct imaging of fluorophores in vivo and advanced techniques such as fluorescence lifetime imaging (FLIM) enable the simultaneous detection of multiple fluorophores. Consequently, it is now possible to record distribution and metabolism of a chemical in vivo and to optimise the delivery of fluorophores in vivo. Recent clinical applications with fluorescein and other intravital fluorescent stains have occurred in neurosurgery, dermatology [including photodynamic therapy (PDT)] and endomicroscopy.

Hepatocellular necrosis, fibrosis and microsomal activity determine the hepatic pharmacokinetics of basic drugs in right-heart-failure-induced liver damage.

Purpose: To explore how liver damage arising from cardio-hepatic syndromes in RHF affect the hepatic pharmacokinetics of basic drugs.

Methods: The hepatic pharmacokinetics of five selected basic drugs with different physicochemical properties were studied in IPRL from control rats and rats with RHF. Hepatic pharmacokinetic modelling was performed with a two-phase physiologically-based organ pharmacokinetic model with the vascular space and dispersion evaluated with the MID technique.

Time-correlated single photon counting for simultaneous monitoring of zinc oxide nanoparticles and NAD(P)H in intact and barrier-disrupted volunteer skin.

Purpose: There is a lack of relevant, non-animal alternatives for assessing exposure and toxicity of nanoparticle-containing cosmetics, e.g. sunscreens.

Changes in antibiotic distribution due to pancreatitis.

This work sought to define how pancreatitis affected antibiotic distribution in a perfused rat pancreas model. The distribution kinetics of four antibiotics were examined in control animals and animals with pancreatitis. Meropenem and piperacillin distributed into the extracellular space, and their distribution kinetics were unaffected by pancreatitis.

Are commercially available nanoparticles safe when applied to the skin?

There are a growing number of commercial uses of nanoparticles which involve direct people contact with the potential for absorption through the skin. Nanoparticles are present in a range of consumer products including colloidal health drinks, carbon fibre sports equipment, sunscreens, cosmetics, electronic products and as antibacterial components of toys, cooking products and wound dressings. Environmental sources of ultra-fine nanoparticles have been present for millennia and anthropogenic sources of similar materials result from industrial processes.

Nanoparticles and microparticles for skin drug delivery.

Skin is a widely used route of delivery for local and systemic drugs and is potentially a route for their delivery as nanoparticles. The skin provides a natural physical barrier against particle penetration, but there are opportunities to deliver therapeutic nanoparticles, especially in diseased skin and to the openings of hair follicles. Whilst nanoparticle drug delivery has been touted as an enabling technology, its potential in treating local skin and systemic diseases has yet to be realised.

Non-invasive imaging of skin physiology and percutaneous penetration using fluorescence spectral and lifetime imaging with multiphoton and confocal microscopy.

New multiphoton and confocal microscope technologies and fluorescence lifetime imaging techniques are now being used to non-invasively image, in space (three dimensions),in time, in spectra, in lifetime and in fluorescence anisotropy (total of 7 dimensions), fluorescent molecules in in situ and in vivo biological tissue, including skin. The process involves scanning a 2D area and measuring fluorescence at a given tissue depth below the surface after excitation by a laser beam with a wavelength within the one-photon or two-photon absorption band of the fluorophores followed by the stacking together of a series of 2D images from different depths to reconstruct the full spatial structure of the sample. Our aim in this work is to describe the principles, opportunities, limitations and applications of this new technology and its application in defining skin morphology, disease and skin penetration in vitro and in vivo by drugs, chemicals and nanoparticles.

Hepatic pharmacokinetics of cationic drugs in a high-fat emulsion-induced rat model of nonalcoholic steatohepatitis.

The hepatic pharmacokinetics of five selected cationic drugs (propranolol, labetalol, metoprolol, antipyrine, and atenolol) was studied in the liver from control rats and from those with high-fat emulsion-induced nonalcoholic steatohepatitis (NASH). Studies were undertaken using an in situ-perfused rat liver and multiple indicator dilution, and outflow data were analyzed with a physiologically based organ pharmacokinetic model. Hepatic extraction (E) was significantly lower in the NASH model, and lipophilicity was the main solute structural determinant of the observed differences in intrinsic elimination clearance (CL(int)) and permeability-surface area product (PS) with pK(a) defining the extent of sequestration in the liver [apparent distribution ratio (K(v))].

Liver fibrosis impairs hepatic pharmacokinetics of liver transplant drugs in the rat model.

This study aims to investigate hepatic pharmacokinetics of the four most common drugs (metoprolol, omeprazole, spironolactone, and furosemide) given to patients undergoing liver transplantation before surgery. The investigation was carried out in CCl(4)-induced fibrotic perfused rat livers and the results were compared to those in normal rat liver. Drug outflow fraction-time profiles were obtained after bolus injection into a single-pass-perfused normal or fibrotic rat liver.

Liver transporters in hepatic drug disposition: an update.

Drug transporters expressed on the hepatocyte membrane play an important role in hepatic drug disposition. In the last two decades, systematic research has resulted in a better understanding of the diversity, expression and substrate specificities of drug transporters in the liver. Here we review recent studies on the role of transporters in drug-drug interactions and disease states such as cirrhosis.

Compatibility studies of acyclovir and lactose in physical mixtures and commercial tablets.

This study documents drug-excipient incompatibility studies of acyclovir in physical mixtures with lactose and in different tablet brands. Differential scanning calorimetry (DSC) was initially used to assess compatibility of mixtures. The Fourier-transform infrared (FTIR) spectrum was also compared with the spectra of pure drug and excipient.

Meropenem dosing in critically ill patients with sepsis and without renal dysfunction: intermittent bolus versus continuous administration? Monte Carlo dosing simulations and subcutaneous tissue distribution.

Objectives: To compare the plasma and subcutaneous tissue concentration-time profiles of meropenem administered by intermittent bolus dosing or continuous infusion to critically ill patients with sepsis and without renal dysfunction, and to use population pharmacokinetic modelling and Monte Carlo simulations to assess the cumulative fraction of response (CFR) against Gram-negative pathogens likely to be encountered in critical care units.

Patients And Methods: We randomized 10 patients with sepsis to receive meropenem by intermittent bolus administration (n = 5; 1 g 8 hourly) or an equal dose administered by continuous infusion (n = 5). Serial subcutaneous tissue concentrations were determined using microdialysis and compared with plasma data for first-dose and steady-state pharmacokinetics.

Acute human self-poisoning with imidacloprid compound: a neonicotinoid insecticide.

Background: Deliberate self-poisoning with older pesticides such as organophosphorus compounds are commonly fatal and a serious public health problem in the developing world. The clinical consequences of self-poisoning with newer pesticides are not well described. Such information may help to improve clinical management and inform pesticide regulators of their relative toxicity.

In vitro and in vivo imaging of xenobiotic transport in human skin and in the rat liver.

Multiphoton tomography was used to examine xenobiotic transport in vivo. We used the photochemical properties of zinc oxide and fluorescein and multiphoton tomography to study their transport in the skin and in the rat liver in vivo. Zinc oxide nanoparticles were visualised in human skin using the photoluminescence properties of zinc oxide and either a selective emission wavelength band pass filter or a filter with fluorescence lifetime imaging (FLIM).

Piperacillin penetration into tissue of critically ill patients with sepsis--bolus versus continuous administration?

Objective: To describe a pharmacokinetic model of piperacillin concentrations in plasma and subcutaneous tissue when administered by bolus dosing and continuous infusion in critically ill patients with sepsis on days 1 and 2 of antibiotic therapy and to compare results against previous results for piperacillin from a cohort of patients with septic shock.

Design: Prospective randomized controlled trial.

Setting: Eighteen-bed intensive care unit at 918-bed tertiary referral hospital.

A preliminary study of atorvastatin plasma concentrations in critically ill patients with sepsis.

Objective: A lack of published pharmacokinetic data on statins in sepsis has prompted concerns about their safety and toxicity. This study determined single dose pharmacokinetics of Atorvastatin administered orally to acutely ill patients.

Design, Setting And Participants: A prospective open label study conducted in a tertiary referral centre on 5 healthy volunteers, 5 acutely ill patients admitted to the medical ward and a heterogeneous cohort of 25 critically ill patients admitted to an intensive care unit.

A novel way to investigate the effects of plasma exchange on antibiotic levels: use of microdialysis.

Plasma exchange (PE) is a treatment modality frequently used for many autoimmune diseases and may cause extracorporeal elimination of antibiotics. No data currently exist on antibiotic concentrations in extracellular fluid during PE. The aim of this study is to describe the effect of PE on the serum and subcutaneous tissue pharmacokinetics of piperacillin administered as a continuous infusion in a critically ill 17-year-old patient with Guillain-Barré syndrome and ventilator-associated pneumonia on Days 1 and 4 of antibiotic therapy.

Subtotal pericardectomy and epicardial excision for treatment of coccidioidomycosis-induced effusive-constrictive pericarditis in dogs: 17 cases (1999-2003).

Objective: To determine the history, clinicopathologic findings, and results of surgery for effusive-constrictive pericarditis associated with Coccidioides immitis infection in dogs.

Design: Retrospective study.

Animals: 17 client-owned dogs that underwent a subtotal pericardectomy and epicardial excision.