Tag Archives | 2011

Modeling of non-stationary RBC survival: Effect of erythropoietin on RBC mortality vs. production in rats.

An age-structured population model was applied to describe red blood cell (RBC) survival data in normal rats treated with recombinant human erythropoietin (rHuEPO). The primary purpose was to estimate the mean lifespan and age of RBCs from a study employing the random labeling technique. The second objective was to assess an impact on the RBC […]

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Missing data

A common challenge for pharmacokinetic modellers is what to do with measurements that are known to be less than the lower limit of quantification (LLOQ). These measurements are, unfortunately, often recorded as BLQ (Below Limit of Quantification), even though the chemical analyst was able to quantify the measurement below this limit. The limit is defined […]

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Is Morphine Clearance Predictable in Humans?

Objectives: To evaluate pharmacokinetic models for prediction of morphine doses from premature neonates to adults. Design: External evaluation of published models for morphine clearance by comparison with literature reports of morphine clearance in individual patients and healthy subjects. Main Outcome Measures: Prediction of morphine dose rate in premature neonates, full term neonates, infants, children and […]

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Population Pharmacokinetic-Pharmacodynamic Modeling: When Modeling Meets Reality

Overview The pharmacokinetic and pharmacodynamic behaviors of many therapeutic agents have inherent complexities that require specialized modeling approaches in order to develop reliable, unbiased models.  Several commonly encountered cases will be presented, including data that has a preponderance of zero values, subjects whose pharmacodynamic trajectories are not predictable based on a structural model, and evaluating models […]

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Population pharmacokinetics of midazolam in critically ill septic patients

The aim of this study is to determine the pharmacokinetic parameters of midazolam (MDZ) and its active metabolites, namely 1-hydroxymidazolam (1-OH-MDZ) and 1-hydroxymidazolam glucuronide conjugate (1-OH-MDZG) in patients with various degrees of severity of sepsis syndrome. A 6-compartment disposition model with combined intermittent oral administration and continuous intravenous infusion with first-order elimination was used. The […]

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Population pharmacokinetic and pharmacodynamics analysis of lipid emulsion propofol in pediatric patients

Aim: This study aimed to characterize the pharmacokinetics and pharmacodynamics of lipid emulsion propofol administered by a target-controlled infusion (TCI) anesthesia in pediatric surgery. Method: Forty patients (ASA PS 1,2) aged 2–12 years were given an intravenous bolus of 2% propofol (Fresofol?, Fresenius Kabi Korea Ltd., Korea) 3 mg/kg, followed by continuous infusion at the rate of 200 mg/kg/min for […]

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Population Pharmacokinetics of Gentamicin in Saudi Newborns during the 1st Week of Life

Introduction: Preterm birth is associated with several complications and serious infections including sepsis. Gentamicin is an important drug approved for the treatment of suspected sepsis and has extensive variable pharmacokinetics in newborns. Objectives: To determine the pharmacokinetic parameters of gentamicin in Saudi newborns population of 92 preterm and term newborns and to identify the covariates that influences […]

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Population Pharmacokinetics of Colistin Methanesulfonate and Formed Colistin in Critically-Ill Patients from a Multi-Center Study Provide Dosing Recommendations for Patients

With increasing clinical emergence of multidrug-resistant Gram-negative pathogens and the paucity of new agents to combat these infections, colistin (administered as its inactive prodrug colistin methanesulfonate (CMS)) has re-emerged as a treatment option especially in critically-ill patients. Previously, there has been a dearth of pharmacokinetic (PK) data available to guide dosing in critically-ill patients including […]

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Statisticians and Pharmacometricians: What can they learn from each other?

Examples are given of how the practice of statistics could be improved if statisticians showed a greater awareness of pharmacokinetic and pharmacodynamic modeling. Some examples are also given where a wider appreciation of statistical theory would improve current approaches to pharmacometrics. Areas in which the two disciplines are in agreement but have failed to have […]

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Missing data – the problem of silent evidence

In his bestseller, The Black Swan, Nassim Nicholas Taleb refers to the problem of silent evidence: the graveyard of failed human endeavour that we never visit. To statisticians this problem is known by the more prosaic title of 'missing data'. I consider some famous examples of misinterpretations arising from missing data and lessons one might […]

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