Nick Hg Holford

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Growth and development can be investigated using readily observable demographic factors such as weight and age. Size is the primary covariate and can be referenced to a 70-kg person with allometry using a coefficient of 0.75 for clearance and 1 for volume. The use of these coefficients is supported by fractal geometric concepts and observations from diverse(More)
Modeling and simulation in general, and specifically clinical trial simulation (CTS), have been recognized by the (larger) pharmaceutical companies and regulatory authorities as being pivotal to improving the efficiency of the drug development process. This includes the use of CTS to learn about drug effectiveness and safety and to optimize trial designs at(More)
The simplest complete system accounting for the time-course of changes in the prothrombin time induced by warfarin requires the combination of 4 independent models: A pharmacokinetic model for the absorption, distribution, and elimination of warfarin. Warfarin is essentially completely absorbed, reaching a maximum plasma concentration between 2 and 6 hours.(More)
BACKGROUND Descriptions of the pharmacokinetics and metabolism of morphine and its metabolites in young children are scant. Previous studies have not differentiated the effects of size from those related to age during infancy. METHODS Postoperative children 0-3 yr old were given an intravenous loading dose of morphine hydrochloride (100 micro g kg(-1) in(More)
This study pools published data to describe the increase in glomerular filtration rate (GFR) from very premature neonates to young adults. The data comprises measured GFR (using polyfructose, 51Cr-EDTA, mannitol or iohexol) from eight studies (n = 923) and involved very premature neonates (22 weeks postmenstrual age) to adulthood (31 years). A nonlinear(More)
Computer simulation of clinical trials has evolved over the past two decades from a simple instructive game to "full" simulation models yielding pharmacologically sound, realistic trial outcomes. The need to make drug development more efficient and informative and the awareness that many industries make extensive use of simulation in product development(More)
Among patients with tuberculosis, rifampin plasma concentrations and sputum conversion rates have been reported to be lower in Africans. Rifampin is a substrate of P-glycoprotein (coded for by the ABCB1 gene) and organic anion-transporting polypeptide 1B1 (coded for by SLCO1B1). The objectives were to identify genetic polymorphisms of drug transporters and(More)
UNLABELLED Remifentanil is a potent opioid with a short duration of action. It has the potential for large-dose opioid anesthesia without an obligatory prolonged period of mechanical ventilation. However, because of high clearance and rapid tissue distribution, cardiopulmonary bypass (CPB) may influence its pharmacokinetics and alter drug requirements. We(More)