The safe use of metformin in heart failure patients both with and without T2DM: A cross-sectional and longitudinal study.

Aims: This study investigated the safe use of metformin in patients with (1) type 2 diabetes mellitus (T2DM) and heart failure on metformin, and (2) heart failure without T2DM and metformin naïve.

Methods: Two prospective studies on heart failure patients were undertaken. The first was a cross-sectional study with two patient cohorts, one with T2DM on metformin (n = 44) and one without T2DM metformin naive (n = 47).

Population pharmacokinetic modelling of febuxostat in healthy subjects and people with gout.

Aims: To investigate and characterise the pharmacokinetics of febuxostat and the effect of the covariates of renal function and body size descriptors on the pharmacokinetics of the drug.

Methods: Blood samples (n = 239) were collected using sparse and rich sampling strategies from healthy (n = 9) and gouty (n = 29) subjects. Febuxostat plasma concentrations were measured by a validated high-performance liquid chromatography method.

Human Group IIA Phospholipase A-Three Decades on from Its Discovery.

Phospholipase A (PLA) enzymes were first recognized as an enzyme activity class in 1961. The secreted (sPLA) enzymes were the first of the five major classes of human PLAs to be identified and now number nine catalytically-active structurally homologous proteins. The best-studied of these, group IIA sPLA, has a clear role in the physiological response to infection and minor injury and acts as an amplifier of pathological inflammation.

Limitations of drug concentrations used in cell culture studies for understanding clinical responses of NSAIDs.

In this review, the in vitro cellular effects of six nonsteroidal anti-inflammatory drugs (NSAIDs), salicylate, ibuprofen, naproxen, indomethacin, celecoxib and diclofenac, are examined. Inhibition of prostanoid synthesis in vitro generally occurs within the therapeutic range of plasma concentrations that are observed in vivo, consistent with the major action of NSAIDs being inhibition of prostanoid production. An additional probable cellular action of NSAIDs has been discovered recently, viz.

Serum concentrations of estriol vary widely after application of vaginal oestriol cream.

Aims: The aim of this study was to establish the pharmacokinetic profile of serum oestriol (E ) concentrations over 24 h following application of vaginal E in chronic users (>12 weeks of E use). The interindividual and intraindividual differences before and after E were examined.

Methods: Ten women participated.

Assessing the accuracy of two Bayesian forecasting programs in estimating vancomycin drug exposure.

Background: Current guidelines for intravenous vancomycin identify drug exposure (as indicated by the AUC) as the best pharmacokinetic (PK) indicator of therapeutic outcome.

Objectives: To assess the accuracy of two Bayesian forecasting programs in estimating vancomycin AUC0-∞ in adults with limited blood concentration sampling.

Methods: The application of seven vancomycin population PK models in two Bayesian forecasting programs was examined in non-obese adults (n = 22) with stable renal function.

A pharmacokinetic-pharmacodynamic study of a single dose of febuxostat in healthy subjects.

Aims: To examine the pharmacokinetic-phamacodynamic (PK-PD) relationships of plasma febuxostat and serum urate and the effect of a single dose of the drug on renal excretion and fractional clearance of urate (FCU).

Methods: Blood and urine samples were collected at baseline and up to 145 hours following administration of febuxostat (80 mg) to healthy subjects (n = 9). Plasma febuxostat and serum and urinary urate and creatinine concentrations were determined.

Better outcomes for patients with gout.

Gout is increasing in prevalence despite effective pharmacotherapies. Barriers to effective management are largely educational deficiencies. Sufferers, usually men, need to understand more about gout, especially that maintaining serum urate below 0.

The safety and pharmacokinetics of metformin in patients with chronic liver disease.

Background: The FDA approved 'label' for metformin lists hepatic insufficiency as a risk for lactic acidosis. Little evidence supports this warning.

Aims: To investigate the safety and pharmacokinetics of metformin in patients with chronic liver disease (CLD).

Comparison of the Area Under the Curve for Vancomycin Estimated Using Compartmental and Noncompartmental Methods in Adult Patients With Normal Renal Function.

Background: Vancomycin pharmacokinetics are best described using a 2-compartment model. However, 1-compartment population models are commonly used as the basis for dose prediction software. Therefore, the validity of using a 1-compartment model to guide vancomycin drug dosing was examined.

Is the use of metformin in patients undergoing dialysis hazardous for life? A systematic review of the safety of metformin in patients undergoing dialysis.

Aims: Metformin may have clinical benefits in dialysis patients; however, its safety in this population is unknown. This systematic review evaluated the safety of metformin in dialysis patients.

Methods: MEDLINE, Embase, CENTRAL, PsycINFO and the Cochrane Library were searched for randomised controlled trials and observational studies evaluating metformin use in dialysis patients.

Determination of febuxostat in human plasma by high performance liquid chromatography (HPLC) with fluorescence-detection.

Febuxostat prevents gout attacks by lowering serum urate. Aspects of the pharmacokinetic-pharmacodynamic relationship of febuxostat concentrations to urate in gout patients need further elucidation. In order to undertake these studies, the assay methodology for febuxostat has been enhanced and validated to meet FDA standards.

Restarting antidepressant and antipsychotic medication after intentional overdoses: need for evidence-based guidance.

Intentional drug overdoses with antidepressant and antipsychotic medications are an increasingly common problem. Currently, there is little guidance with regard to reintroduction of these medications after intentional overdoses. We have used published toxicological and pharmacokinetic data to obtain factors which control the recovery from overdoses.

Predicting Response or Non-response to Urate-Lowering Therapy in Patients with Gout.

Purpose Of Review: To review the extent of treatment success or failure with the xanthine oxidoreductase inhibitors allopurinol and febuxostat and indicate how the dosage of urate-lowering therapy (ULT) may be modified to increase the response in the majority of patients with gout.

Recent Findings: Gout flares are associated with serum concentrations of urate above 0.42 mmol/L (7 mg/dL).

Individualising the dose of allopurinol in patients with gout.

Aims: The aims of the study were to: 1) determine if a plasma oxypurinol concentration-response relationship or an allopurinol dose-response relationship best predicts the dose requirements of allopurinol in the treatment of gout; and 2) to construct a nomogram for calculating the optimum maintenance dose of allopurinol to achieve target serum urate (SU) concentrations.

Methods: A nonlinear regression analysis was used to examine the plasma oxypurinol concentration- and allopurinol dose-response relationships with serum urate. In 81 patients (205 samples), creatinine clearance (CL ), concomitant diuretic use and SU concentrations before (U ) and during (U ) treatment were monitored across a range of allopurinol doses (D, 50-700 mg daily).

Allopurinol: insights from studies of dose-response relationships.

Gout is the most common inflammatory arthritis in men and is increasingly prevalent. Allopurinol is very effective at reducing plasma urate concentrations to a level sufficient to dissolve monosodium urate crystals. However, many patients fail to achieve a sufficient therapeutic response to allopurinol.

Xanthine oxidoreductase and its inhibitors: relevance for gout.

Xanthine oxidoreductase (XOR) is the rate-limiting enzyme in purine catabolism and converts hypoxanthine to xanthine, and xanthine into uric acid. When concentrations of uric acid exceed its biochemical saturation point, crystals of uric acid, in the form of monosodium urate, emerge and can predispose an individual to gout, the commonest form of inflammatory arthritis in men aged over 40 years. XOR inhibitors are primarily used in the treatment of gout, reducing the formation of uric acid and thereby, preventing the formation of monosodium urate crystals.

Clinical Pharmacokinetics and Pharmacodynamics of Febuxostat.

Febuxostat is a xanthine oxidoreductase inhibitor that has been developed to treat chronic gout. In healthy subjects, the pharmacokinetic parameters of febuxostat after multiple oral dose administration include an oral availability of about 85 %, an apparent oral clearance (CL/F) of 10.5 ± 3.

Multiple episodes of aspirin overdose in an individual patient: a case report.

Introduction: Aspirin overdose, though now infrequently encountered, nevertheless continues to contribute to significant morbidity and mortality. The patient described in this case report intentionally ingested overdoses of aspirin on repeated occasions. The case provided an unusual and possibly one-of-a-kind opportunity to focus on the variability in the time course of plasma salicylate concentrations with current treatment modalities of aspirin overdose in an individual patient.