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Population pharmacokinetics of abacavir in infants, toddlers and children.

ABSTRACT: To characterize the pharmacokinetics of abacavir in infants, toddlers and children and to assess the influence of covariates on drug disposition across these populations.Abacavir concentration data from three clinical studies in human immunodeficiency virus-infected children (n = 69) were used for model building. The children received either a weight-normalized dose of 16 mg kg(-1) day(-1) or the World Health Organization recommended dose based on weight bands. A population pharmacokinetic analysis was performed using nonlinear mixed effects modelling VI. The influence of age, gender, bodyweight and formulation was evaluated. The final model was selected according to graphical and statistical criteria.A two-compartmental model with first-order absorption and first-order elimination best described the pharmacokinetics of abacavir. Bodyweight was identified as significant covariate influencing the apparent oral clearance and volume of distribution. Predicted steady-state maximal plasma concentration and area under the concentration-time curve from 0 to 12 h of the standard twice daily regimen were 2.5 mg l(-1) and 6.1 mg h l(-1) for toddlers and infants, and 3.6 mg l(-1) and 8.7 mg h l(-1) for children, respectively. Model-based predictions showed that equivalent systemic exposure was achieved after once and twice daily dosing regimens. There were no pharmacokinetic differences between the two formulations (tablet and solution). The model demonstrated good predictive performance for dosing prediction in individual patients and, as such, can be used to support therapeutic drug monitoring in conjunction with sparse sampling.The disposition of abacavir in children appears to be affected only by differences in size, irrespective of the patient's age. Maturation processes of abacavir metabolism in younger infants should be evaluated in further studies to demonstrate the potential impact of ontogeny.

SUBMITTER: Zhao W

PROVIDER: S-EPMC3690111 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Population pharmacokinetics of abacavir in infants, toddlers and children.

Zhao Wei W Piana Chiara C Danhof Meindert M Burger David D Della Pasqua Oscar O Jacqz-Aigrain Evelyne E

British journal of clinical pharmacology 20130601 6

<h4>Aims</h4>To characterize the pharmacokinetics of abacavir in infants, toddlers and children and to assess the influence of covariates on drug disposition across these populations.<h4>Methods</h4>Abacavir concentration data from three clinical studies in human immunodeficiency virus-infected children (n = 69) were used for model building. The children received either a weight-normalized dose of 16 mg kg(-1) day(-1) or the World Health Organization recommended dose based on weight bands. A pop ...[more]

PMID: 23126277

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Project description:BackgroundMany updates to young child feeding recommendations have been published over the past decade, but concurrent intake trends have not been assessed.ObjectiveThe aim of this study was to evaluate adequacy and trends in energy and nutrient intakes of US infants and children aged 0-47.9 mo through use of Feeding Infants and Toddlers Study (FITS) data from 2002, 2008, and 2016.MethodsFITS are cross-sectional surveys of parents/caregivers of infants and young children (FITS 2002, n = 2962; FITS 2008, n = 3276; FITS 2016, n = 3235). Dietary intakes were assessed by telephone with trained interviewers using the Nutrition Data System for Research. Mean ± SE nutrient intakes were calculated. Diet adequacy was assessed with the nutrient adequacy ratio (NAR) for 17 nutrients and the corresponding mean adequacy ratio.ResultsEnergy and macronutrient intakes were generally stable across surveys, but significant decreases for saturated fat and total sugars and an increase in fiber were observed among 6-11.9-mo-olds and 12-23.9-mo-olds (P-trend < 0.0001). Mean sodium intakes exceeded Adequate Intakes (AI) for all ages, whereas fiber intakes were universally below the AI. Nutrients with the lowest NAR values were vitamin D (range 0.41-0.67/1.00) and vitamin E (range 0.60-0.79/1.00 for 2008 and 2016). For iron, infants aged 6-11.9 mo had the lowest NAR values at 0.77-0.88/1.00, compared to 0.85-0.89/1.00 for 12-47.9-mo-olds. Potassium was low from 12 to 47.9 mo (NAR range 0.55-0.63/1.00 across survey years). The nutrients with the greatest decline in mean intakes were iron and vitamins D and E among 6-11.9-mo-olds, and vitamin D and potassium among 12-23.9-mo-olds in 2016 compared to 2002.ConclusionsThe diets of US infants and young children were generally adequate for most micronutrients and stable over time, but sodium intakes were too high, and nutrient gaps still existed, especially for vitamins D, E, and fiber across ages and for iron among infants.

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Dataset Information

Population pharmacokinetics of abacavir in infants, toddlers and children.

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Population pharmacokinetics of abacavir in infants, toddlers and children.

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