Publications by authors named "Begg E"

Objectives: We evaluated the effects of probenecid on the Pharmaco Kinetics (PK) and pharmacodynamics (PD) of oral cephalexin in healthy volunteers.

Methods: Cephalexin 1000 mg was administered orally to 11 healthy volunteers following a standardized meal, with and without probenecid 500 mg orally, on two separate days one week apart. Total plasma concentrations of cephalexin and probenecid over a 12 h period were measured by liquid chromatography tandem mass spectrometry.

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A key issue in neurobiological studies of episodic-like memory is the geometric frame of reference in which memory traces of experience are stored. Assumptions are sometimes made that specific protocols favour either allocentric (map-like) or egocentric (body-centred) representations. There are, however, grounds for suspecting substantial ambiguity about coding strategy, including the necessity to use both frames of reference occasionally, but tests of memory representation are not routinely conducted.

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Objectives: To measure the effect of probenecid, fasting and fed, on flucloxacillin pharmacokinetic and pharmacodynamic endpoints.

Methods: Flucloxacillin 1000 mg orally was given to 11 volunteers alone while fasting ('flucloxacillin alone'), and with probenecid 500 mg orally while fasting ('probenecid fasting') and with food ('probenecid fed'). Flucloxacillin pharmacokinetic and pharmacodynamic endpoints were compared.

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We have evaluated the literature to review optimal dosing and monitoring of intravenous vancomycin in adults, in response to evolving understanding of targets associated with efficacy and toxicity. The area under the total concentration-time curve (0-24 h) divided by the minimum inhibitory concentration (AUC/MIC) is the most commonly accepted index to guide vancomycin dosing for the treatment of Staphylococcus aureus infections, with a value of 400 h a widely recommended target for efficacy. Upper limits of AUC exposure of around 700 (mg/L).

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Background: Pharmacokinetic studies and therapeutic drug monitoring of antibiotics require a simple, rapid, and reliable analytical method for monitoring the concentrations in plasma, including unbound concentrations for highly protein-bound drugs. The aim of the current work was to develop and validate a liquid chromatography-tandem mass spectrometry method for the simultaneous determination of total and unbound concentrations of 3 widely used β-lactam antibiotics (cefalexin, cefazolin, and flucloxacillin) and the often coadministered drug probenecid in human plasma, suitable for pharmacokinetic studies and for routine use in ordinary, busy hospital laboratories.

Methods: Unbound drug was separated from bound drug by ultrafiltration.

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It is usually recommended that flucloxacillin is given on an empty stomach. The aim of this study was to compare total and free flucloxacillin concentrations after oral flucloxacillin, given with and without food, based on contemporary pharmacokinetic and pharmacodynamic targets. Flucloxacillin 1000 mg orally was given to 12 volunteers, after a standardised breakfast and while fasting, on two separate occasions.

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Aims: Flucloxacillin dosing may be guided by measurement of its total plasma concentrations. Flucloxacillin is highly protein bound with fraction unbound in plasma (f ) of around 0.04 in healthy individuals.

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Aims: We aimed to compare the performances of contemporary cystatin C (Cys)-based GFR equations, and the creatinine only Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for predicting gentamicin clearance.

Methods: The bias and imprecision of the CKD-EPI, CKD-EPI_Cys and creatinine-cystatin C CKD-EPI (CKD-EPI_CrCys) equations for predicting gentamicin clearances, were assessed in 260 patients treated with gentamicin during 2012-2013. The creatinine-cystatin C Berlin Initiative Study equation (BIS_CrCys) was examined in the ≥70 year subgroup.

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Background: Extended interval dosing (EID) of gentamicin most commonly involves dosing every 24 hours, but patients with impaired renal function may require a longer dose interval. This study examines a large database of patients treated with gentamicin from 1996 to 2010 to see how many patients with renal impairment would have benefited from dose intervals >24 hours and to define the incidence of nephrotoxicity.

Methods: All patients aged ≥ 16 years who had received gentamicin by EID over the 14-year period and had concentration data available were examined.

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Aims: Dabigatran is largely cleared by renal excretion. Renal function is thus a major determinant of trough dabigatran concentrations, which correlate with the risk of thromboembolic and haemorrhagic outcomes. Current dabigatran dosing guidelines use the Cockcroft-Gault (CG) equation to gauge renal function, instead of contemporary equations including the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations employing creatinine (CKD-EPI_Cr), cystatin C (CKD-EPI_Cys) and both renal biomarkers (CKD-EPI_CrCys).

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Aims: Population pharmacokinetic (pop PK) modelling can be used for PK assessment of drugs in breast milk. However, complex mechanistic modelling of a parent and an active metabolite using both blood and milk samples is challenging. We aimed to develop a simple predictive pop PK model for milk concentration-time profiles of a parent and a metabolite, using data on fluoxetine (FX) and its active metabolite, norfluoxetine (NFX), in milk.

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Aims: In patients with atrial fibrillation prescribed dabigatran, the aim was to examine the correlation between plasma dabigatran concentrations and the three screening coagulation assays [international normalized ratio (INR), activated partial thromboplastin time (aPTT) and thrombin time (TT)] as well as the dilute thrombin time (dTT) and to examine the contribution of plasma fibrinogen concentrations to the variability in TT results.

Methods: Plasma from patients with atrial fibrillation on dabigatran were analysed for clotting times and concentrations of fibrinogen and dabigatran. Correlation plots (and associated r(2) values) were generated using these data.

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Dabigatran is an oral anticoagulant that is increasingly used for atrial fibrillation (AF). Presently, many authorities state that routine laboratory coagulation monitoring is not required. However, data have recently been published demonstrating that higher trough plasma dabigatran concentrations are associated with lower thromboembolic and higher haemorrhagic event rates.

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Background: A busulfan concentration monitoring and dosing service has been provided by Christchurch Hospital since 1998. This study aimed to see (1) the percentage of patients with an area under the concentration time curve (AUC) outside the target range and had dose adjustment, (2) how busulfan clearance (CL) relates to body weight, and (3) if fewer samples could be used to predict doses.

Methods: Blood samples were taken from patients after oral administration, usually at 0.

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Background: It is unclear which renal function equation, employing an isotope dilution mass spectrometry (IDMS)-aligned creatinine assay, best predicts gentamicin clearance.

Methods: The performances of the Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD) Study and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations for predicting gentamicin clearances were assessed retrospectively in 240 patients treated with gentamicin during 2011-2012, when the local creatinine assay was IDMS-aligned. Comparisons were based on the percentage within 30% of gentamicin clearance (P 30) and the root-mean-square error (RMSE) of each equation.

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Background: Plasma concentrations of the anticoagulant dabigatran are correlated with clinical outcomes, and are affected by renal function, intestinal P-glycoprotein (P-gp) activity and stomach acidity.

Aims: To determine the adherence to dabigatran etexilate renal dosing guidelines, the frequency of co-prescription of potentially interacting drugs in patients on dabigatran, and how these related to dabigatran dosing.

Methods: A retrospective chart review of 204 patients discharged from a tertiary hospital on dabigatran etexilate over a 12-month period.

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To the best of our knowledge, there have been no published studies of doxazosin transfer into human milk. In rats, milk concentrations twentyfold higher than in plasma have been reported. Based on these animal data, some references advise to avoid breastfeeding during doxazosin therapy.

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Background: Current Australian guidelines recommend initiating directed therapy of gentamicin if administration exceeds 48 h. Directed doses of gentamicin require the monitoring of plasma concentrations of gentamicin to determine the 24-h area under the time course of plasma gentamicin concentrations (AUC) and a dosage prediction program, for example TCIWorks or Aladdin. However, doses calculated by such programs have not been compared with an established program.

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A rapid and simple high-performance liquid chromatography (HPLC) assay was developed for the simultaneous determination of three triazole antifungals (voriconazole, posaconazole, and itraconazole and the metabolite of itraconazole, hydroxyitraconazole) in human plasma. Sample preparation involved a simple one-step protein precipitation with 1.0 M perchloric acid and methanol.

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Imatinib is a first-line treatment for chronic myelogenous leukaemia (CML). The pharmacokinetics of imatinib in patients with CML are characterised by large interpatient variability. Concentration monitoring of imatinib and its active metabolite N-desmethyl imatinib (DMI) is considered necessary to enhance the safe and effective use of imatinib.

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