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.

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.

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.

Effectiveness of an electronic patient-centred self-management tool for gout sufferers: a cluster randomised controlled trial protocol.

Introduction: Gout is increasing despite effective therapies to lower serum urate concentrations to 0.36 mmol/L or less, which, if sustained, significantly reduces acute attacks of gout. Adherence to urate-lowering therapy (ULT) is poor, with rates of less than 50% 1 year after initiation of ULT.

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).

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.

Understanding the dose-response relationship of allopurinol: predicting the optimal dosage.

Aims: The aim of the study was to identify and quantify factors that control the plasma concentrations of urate during allopurinol treatment and to predict optimal doses of allopurinol.

Methods: Plasma concentrations of urate and creatinine (112 samples, 46 patients) before and during treatment with various doses of allopurinol (50-600 mg daily) were monitored. Non-linear and multiple linear regression equations were used to examine the relationships between allopurinol dose (D), creatinine clearance (CLcr) and plasma concentrations of urate before (UP) and during treatment with allopurinol (UT).

Reactive joint symptoms following an outbreak of Salmonella typhimurium phage type 135a.

Objective: To quantify the incidence and clinical features of reactive arthritis (ReA) developing in a cohort exposed to an outbreak of Salmonella typhimurium phage type 135a, and factors affecting host susceptibility to ReA.

Methods: A screening questionnaire was mailed to 493 patients with confirmed Salmonella infection. Musculoskeletal symptoms and extraarticular manifestations of ReA were quantified.