Archive | Abstracts

Comparison of different diagnostic criterion to evaluate nonlinear mixed-effects models

Background: The use of conditional weighted residual (CWRES) and post-hoc ETA (ηph) distribution properties, instead of weighted residual (WRES) distribution properties, as model diagnostic tools when using the first-order conditional (FOCE) algorithm in NONMEM, may give a more accurate picture of if and when a model is miss-specified. Aim: A simulation study was performed to compare these […]

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Nonlinear Mixed Effects Modeling of the Steady-State Pharmacokinetics (PK) of Tipranavir/Ritonavir 500/200 mg bid (TPV/r) for Adult Healthy Volunteers and HIV+ Patients

Background: TPV is the first of a new class of non-peptidic PIs, and has potent activity against multiple PI-resistant HIV. To enhance TPV PK, it is combined with low-dose ritonavir. This abstract reports the results of nonlinear mixed effects modeling to characterize the PK of TPV and to elucidate the effects of demographic parameters on the population […]

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Optimal Designs of Studying Bioimpedance – Design for Nonlinear Mixed Effects Models

Bioelectrical impedance analysis measures the impedance to flow of an alternating electrical current passed through biological tissue. Such impedance measurements allow one to estimate fat-free body mass which is an accepted estimate for lean body weight, considered by some to be a better predictor of drug clearance in the obese than, for example, total body […]

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Different ways of incorporating data below the quantification limit in datasets for parameter estimation

Background: The handling of data below the lower limit of quantification (LLOQ) and the limit of detection (LOD) continues to be a challenge in pharmacokinetic analyses. The LLOQ is the lowest concentration of an analyte in a sample which can be measured with a predefined acceptable level of accuracy and precision (± 20 %). Whereas the […]

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Population Pharmacokinetics of Amikacin in Very Premature Malaysian Neonates

Background: Amikaicn is an aminoglycoside used in the treatment of early onset neonatal sepsis. Nephrotoxicity and ototoxicty induced by aminoglycosides are closely associated with the duration of treatment and the high plasma peak or trough levels. Therapeutic drug monitoring of amikacin has routinely been carried out in neonatal intensive units. Aim: To characterize the population pharmacokinetic parameters […]

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Population Pharmacokinetics of Oral and Intravenous Caffeine in Extremely Premature Neonates

Background: Apnea of prematurity (AP) is a potentially serious condition in >90% of extremely premature neonates. It is characterized by the cessation of airways movements for 15-20 seconds or more and, if left untreated, can have serious sequelae. Caffeine (citrate salt) is now the drug of choice for helping wean premature infants from mechanical ventilation, but […]

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Maximum likelihood estimation in nonlinear mixed effects models with the SAEM algorithm

The statistical model for most population PK/PD analyses is the nonlinear-mixed effects model (NLMEM). As opposed to linear models, there are statistical issues to express the optimisation criteria for these nonlinear models so that first approximation methods (FO and FOCE) based on linearization of the model were proposed. It is well known that these methods […]

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Population Pharmacokinetics of Phase 1/2a Data After Oral Tablet Administration of Maraviroc

Background: Maraviroc, an antagonist of the human chemokine receptor CCR5, is being developed for the treatment of HIV-1 infection. Previous findings showed a disproportional increase in AUC with increasing doses and food effects on both bioavailability (F) and absorption rate constant (ka). The aim of this analysis was to describe the population pharmacokinetics (PK) of maraviroc […]

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