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Residual Variability (residual + variability)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

Mapping sea bird densities over the North Sea: spatially aggregated estimates and temporal changes

ENVIRONMETRICS, Issue 6 2005
Edzer J. Pebesma
Abstract In the Dutch sector of the North Sea, sea bird densities are recorded bi-monthly by using airborne strip-transect monitoring. From these data we try to estimate: (i) high-resolution spatial patterns of sea bird densities; (ii) low-resolution spatial-average bird densities for large areas; and (iii) temporal changes in (i) and (ii), using data on Fulmaris glacialis as an example. For spatial estimation, we combined Poisson regression for modelling the trend as a function of water depth and distance to coast with kriging interpolation of the residual variability, assuming spatial (co)variances to be proportional to the trend value. Spatial averages were estimated by block kriging. For estimating temporal differences we used residual cokriging for two consecutive years, and show how this can be extended to analyse trends over multiple years. Approximate standard errors are obtained for all estimates. A comparison with a residual simple kriging approach reveals that ignoring temporal cross-correlations leads to a severe loss of statistical accuracy when assessing the significance of temporal changes. This article shows results for Fulmaris glacialis monitored during August/September in 1998 and 1999. Copyright © 2005 John Wiley & Sons, Ltd. [source]

The pharmacokinetics of idraparinux, a long-acting indirect factor Xa inhibitor: population pharmacokinetic analysis from Phase III clinical trials

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 4 2009
C. VEYRAT-FOLLET
Summary.,Background: Idraparinux, a long-acting synthetic pentasaccharide, is a specific antithrombin-dependent inhibitor of activated factor X that has been investigated in the treatment and prevention of thromboembolic events. Objectives: To characterize the population pharmacokinetic profile of idraparinux in patients enrolled in van Gogh and Amadeus Phase III clinical trials. Patients and methods: Idraparinux was administered once-weekly subcutaneously at a dose of 2.5 mg, or 2.5 mg (first dose) and then 1.5 mg for patients with severe renal insufficiency (creatinine clearance <30 mL min,1). A population pharmacokinetic model was developed using data from 704 patients with acute deep-vein thrombosis or pulmonary embolism, 1310 patients suffering from atrial fibrillation, and 40 healthy subjects. Potential covariates analyzed included demographics (age, sex, weight and ethnicity), and serum creatinine and creatinine clearance determinations. Results: A three-compartment model best described idraparinux pharmacokinetics, with interindividual variability on clearance, central volume of distribution, and absorption rate constant; residual variability was low. Typical clearance, central volume of distribution, absorption rate constant and volume of distribution at steady-state were 0.0255 L h,1, 3.36 L, 1.37 h and 30.8 L, respectively. Peak concentration was reached at 2.5 h. The terminal half-life was 66.3 days and time to steady-state was 35 weeks. At steady-state, exposures were similar for patients without and with severe renal impairment receiving adjusted-dose. Creatinine clearance was the most important covariate affecting idraparinux clearance. The particular characteristics of idraparinux , rapid onset of action and long-acting anticoagulant effect , offer interesting clinical perspectives currently under investigation with idrabiotaparinux, the reversible biotinylated form of idraparinux. [source]

Population pharmacokinetics of valproate in Mexican children with epilepsy

BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 9 2008
Tania Correa
Abstract Background. The aim of this study was to determine the factors that influence valproate clearance (CL) in Mexican epileptic pediatric patients using a mixed-effect model and sparse data of serum concentrations of valproic acid (VPA) collected during routine clinical care of patients. Methods. The number of patients included in the study was 110. The population CL was calculated by using the NONMEM program. The following covariates were tested by their influence on CL: total body weight (TBW), height, age, body surface area, daily dose (DD), sex of the patient and comedication with phenobarbital (PB) or carbamazepine. Results. The final regression model for valproic CL found best to describe the data was: CL/F=(0.0466+0.00363 TBW+0.000282 DD) * (1+0.236 PB). This model allows a reduction of 50% of the interindividual variability and of 31% of the residual variability described by the basic model that does not include covariables. Conclusions. Total body weight, daily dose of valproate and concomitant therapy with PB are factors that significantly influence VPA kinetic disposition and they should be considered in programming dosage regimens for this antiepileptic drug in the pediatric population. The validation of the model supports its acceptability for clinical purposes. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Pharmacokinetics of ribavirin in patients with hepatitis C virus

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 6 2006
Janet R. Wade
Aim A population pharmacokinetic analysis was performed using plasma concentration data (n = 7025) from 380 patients to examine the relationship between ribavirin dose and its pharmacokinetics. Methods Ribavirin pharmacokinetics were described by a three-compartment model with sequential zero-order and a first-order absorption processes. Interoccasion variability and food effects were included. Results Lean body weight (range 41,91 kg) was the only covariate with a clinically significant influence on ribavirin pharmacokinetics, affecting clearance (15.3,23.9 l h,1) and the volume of the larger peripheral compartment. Conclusion The model provided a good description of the available data, confirmed by accurate estimates of parameter values and low residual variability (17%). [source]