Nick Holford

Author Archive | Nick Holford

Twenty Years of PAGANZ

The PAGANZ 2019 meeting in Auckland celebrates the twentieth PAGANZ meeting held in Australasia. The original speakers at PAGANZ in 1999 who are also present at PAGANZ 2019 reflects the beneficial effect of pharmacometrics on longevity and friendship. Pharmacometrics is the boom growth field in clinical pharmacology. It has other names which serve local purposes […]

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A Population Pharmacodynamic Study of Apnea of Prematurity and the Effect of Caffeine Citrate in Chinese Premature Neonates

Objective: Apnea of prematurity (AOP) is defined as an attack of apnea for at least 20 seconds, with bradycardia and cyanosis. It is a common phenomenon in the neonatal intensive care unit (NICU). Caffeine is used to suppress or to prevent AOP attacks. Based on a population pharmacokinetic (PK) model for caffeine the effect of caffeine […]

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ANZDATA: Pharmacology based time to event analysis for death and renal transplant failure

Background: The ANZDATA registry (http://www.anzdata.org.au/v1) has collected data on all patients receiving a renal transplant in Australia or New Zealand since 1977  Objective: To describe the effect of immunosuppressant medicines on time to death and time to renal transplant failure Methods: Demographic data and the daily dose of medicines used as immunosuppressants were extracted from […]

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NextDose – A web based dosing tool – Development version 2017

Background: NextDose is a web based Bayesian dosing tool (1, 2). Dosing guidance is currently offered for intravenous busulfan, intravenous methotrexate and oral tacrolimus. It has been used at Auckland Starship Hospital and Auckland City Hospital to guide dosing of busulfan since 2012 (3). Objectives: 1. To describe the features of a new release of […]

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Systems Pharmacology – Learning from GAVamycin

Background: “Systems pharmacology is the application of systems biology principles to the field of pharmacology.”(1). The pharmacokinetics of gentamicin (G), amikacin (A) and vancomycin (V) have been widely described including models with common features for each drug (2, 3) and a proposal to predict glomerular filtration rate (GFR) from drug clearance (CL). A reverse systems […]

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Busulfan Target Concentration Intervention Audit and Model Evaluation

Background: Intravenous busulfan is used prior to haematopoetic stem cell transplantation. All patients undergoing this procedure in New Zealand since 2012 have been treated in Auckland. A web based target concentration intervention tool (NextDose) has been used by the clinical laboratory. Demographic, dosing and concentration details and desired target concentration or target area under the […]

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Evaluation of NONMEM 7.3.0 and Monolix 4.2.2 by Parametric Bootstrap

Evaluation of NONMEM 7.3.0 and Monolix 4.2.2 by Parametric Bootstrap Nick Holford, University of Auckland NONMEM 7.3.0 and Monolix 4.2.2 were evaluated in terms of parameter estimation bias and uncertainty coverage bias using a parametric bootstrap procedure. All calculations were performed using the NeSI PAN cluster. Four problems of increasing difficulty were tested: warfarin pharmacokinetics, […]

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Busulfan pharmacokinetics in neonates, infants, children and adults

Purpose: We have developed a pharmacokinetic model of intravenous (IV) busulfan that is applicable from neonates to adults that accounts for differences in size, body composition and age. Experimental design: Routinely collected busulfan concentration profiles were obtained at a national center for measuring busulfan concentrations. Dosing and demographic data was matched with 12,380 concentrations in […]

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A clinical trial incident: Why simple PK is sometimes not so simple

The antibiotic dose calculator trial in children aims to find out if a web based dose calculator is better than department protocols used in 3 clinical units for achieving target concentrations of amikacin, gentamicin or vancomycin.  During the trial an incident occurred when the dose calculator dose proposed a clearly inappropriate maintenance dose and dosing […]

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What is the between cycle variability in methotrexate clearance?

Background High dose methotrexate (MTX) is the mainstay of treatment for many cancers. It is typically administered on repeated occasions known as ‘cycles’.  Due to extensive variability in its pharmacokinetics (PK) and life-threatening toxicity, the use of repeated MTX concentration measurements to determine the duration of  leucovorin dosing has decreased the incidence of severe toxicity.  […]

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