Population Pharmacokinetics of Olanzapine in Children

Aims The aim of this study was to evaluate the population pharmacokinetics (PopPK) of olanzapine in children and devise a model-informed paediatric dosing scheme. Methods The PopPK of olanzapine was characterized using opportunistically collected plasma samples from children receiving olanzapine per standard of care for any indication. A nonlinear mixed effect modelling approach was employed for model development using the software NONMEM (v7.4). Simulations from the developed PopPK model were used to devise a paediatric dosing scheme that targeted comparable plasma exposures to adolescents and adults. Results Forty-five participants contributed 83 plasma samples towards the analysis. The median (range) postnatal age and body weight of participants were 3.8 years (0.2–19.2) and 14.1 kg (4.2–111.7), respectively. The analysis was restricted to pharmacokinetic (PK) samples collected following enteral administration (oral and feeding tube). A one-compartment model with linear elimination provided an appropriate fit to the data. The final model included the covariates body weight and postmenstrual age (PMA) on apparent olanzapine clearance (CL/F). Typical CL/F and apparent volume of distribution (scaled to 70 kg) were 16.8 L/h (21% RSE) and 663 L (13% RSE), respectively. Developed dosing schemes used weight-normalized doses for children ≤6 months postnatal age or \u3c15 kg and fixed doses for children ≥15 kg. Conclusion We developed a paediatric PopPK model for enterally-administered olanzapine. To our knowledge, this analysis is the first study to characterize the PK of olanzapine in participants ranging from infants to adolescents. Body weight and PMA were identified as influential covariates for characterizing developmental changes in olanzapine apparent clearance

Solithromycin Pharmacokinetics in Plasma and Dried Blood Spots and Safety in Adolescents

ABSTRACT We assessed the pharmacokinetics and safety of solithromycin, a fluoroketolide antibiotic, in a phase 1, open-label, multicenter study of 13 adolescents with suspected or confirmed bacterial infections. On days 3 to 5, the mean (standard deviation) maximum plasma concentration and area under the concentration versus time curve from 0 to 24 h were 0.74 μg/ml (0.61 μg/ml) and 9.28 μg · h/ml (6.30 μg · h/ml), respectively. The exposure and safety in this small cohort of adolescents were comparable to those for adults. (This study has been registered at ClinicalTrials.gov under registration no. NCT01966055.

The Impact of Short Stature on Health-Related Quality of Life in Children with Chronic Kidney Disease

To compare the health-related quality of life (HRQoL) of children with CKD and short stature (SS) to children with CKD and normal height (NH), to evaluate the impact of catch up growth and growth hormone use on HRQoL, and to describe the concordance of perceptions of HRQoL between children with SS and NH and their parents

Depressive Symptoms in Children with Chronic Kidney Disease

To assess depression in children with chronic kidney disease (CKD) and to determine associations with patient characteristics, intellectual and educational levels, and health related quality of life (HRQoL)

Population Pharmacokinetics of Olanzapine in Children

Aims The aim of this study was to evaluate the population pharmacokinetics (PopPK) of olanzapine in children and devise a model-informed paediatric dosing scheme. Methods The PopPK of olanzapine was characterized using opportunistically collected plasma samples from children receiving olanzapine per standard of care for any indication. A nonlinear mixed effect modelling approach was employed for model development using the software NONMEM (v7.4). Simulations from the developed PopPK model were used to devise a paediatric dosing scheme that targeted comparable plasma exposures to adolescents and adults. Results Forty-five participants contributed 83 plasma samples towards the analysis. The median (range) postnatal age and body weight of participants were 3.8 years (0.2–19.2) and 14.1 kg (4.2–111.7), respectively. The analysis was restricted to pharmacokinetic (PK) samples collected following enteral administration (oral and feeding tube). A one-compartment model with linear elimination provided an appropriate fit to the data. The final model included the covariates body weight and postmenstrual age (PMA) on apparent olanzapine clearance (CL/F). Typical CL/F and apparent volume of distribution (scaled to 70 kg) were 16.8 L/h (21% RSE) and 663 L (13% RSE), respectively. Developed dosing schemes used weight-normalized doses for children ≤6 months postnatal age or \u3c15 kg and fixed doses for children ≥15 kg. Conclusion We developed a paediatric PopPK model for enterally-administered olanzapine. To our knowledge, this analysis is the first study to characterize the PK of olanzapine in participants ranging from infants to adolescents. Body weight and PMA were identified as influential covariates for characterizing developmental changes in olanzapine apparent clearance

Solithromycin Pharmacokinetics in Plasma and Dried Blood Spots and Safety in Adolescents

We assessed the pharmacokinetics and safety of solithromycin, a fluoroketolide antibiotic, in a phase 1, open-label, multicenter study of 13 adolescents with suspected or confirmed bacterial infections. On days 3 to 5, the mean (standard deviation) maximum plasma concentration and area under the concentration versus time curve from 0 to 24 h were 0.74 μg/ml (0.61 μg/ml) and 9.28 μg · h/ml (6.30 μg · h/ml), respectively. The exposure and safety in this small cohort of adolescents were comparable to those for adults. (This study has been registered at ClinicalTrials.gov under registration no. NCT01966055.

Population Pharmacokinetics of Olanzapine in Children

Aims The aim of this study was to evaluate the population pharmacokinetics (PopPK) of olanzapine in children and devise a model-informed paediatric dosing scheme. Methods The PopPK of olanzapine was characterized using opportunistically collected plasma samples from children receiving olanzapine per standard of care for any indication. A nonlinear mixed effect modelling approach was employed for model development using the software NONMEM (v7.4). Simulations from the developed PopPK model were used to devise a paediatric dosing scheme that targeted comparable plasma exposures to adolescents and adults. Results Forty-five participants contributed 83 plasma samples towards the analysis. The median (range) postnatal age and body weight of participants were 3.8 years (0.2–19.2) and 14.1 kg (4.2–111.7), respectively. The analysis was restricted to pharmacokinetic (PK) samples collected following enteral administration (oral and feeding tube). A one-compartment model with linear elimination provided an appropriate fit to the data. The final model included the covariates body weight and postmenstrual age (PMA) on apparent olanzapine clearance (CL/F). Typical CL/F and apparent volume of distribution (scaled to 70 kg) were 16.8 L/h (21% RSE) and 663 L (13% RSE), respectively. Developed dosing schemes used weight-normalized doses for children ≤6 months postnatal age or \u3c15 kg and fixed doses for children ≥15 kg. Conclusion We developed a paediatric PopPK model for enterally-administered olanzapine. To our knowledge, this analysis is the first study to characterize the PK of olanzapine in participants ranging from infants to adolescents. Body weight and PMA were identified as influential covariates for characterizing developmental changes in olanzapine apparent clearance

A Weight Estimation Strategy for Preterm and Full-Term Infants

Weight is the foremost marker of health outcomes in infants; however, the majority of community workers and health care providers in remote, resource-constrained settings have limited access to functional scales. This study develops and validates a simple weight estimation strategy for infants that addresses the limitations of current approaches. Circumferential and segmental anthropometric measures were evaluated for their relationship to infant weight and length. Data derived from 2097 US infants (n = 1681 for model development, n = 416 for validation). Statistical and practical considerations informed final measurement selection. Head circumference and chest circumference demonstrated the best correlations with weight ( r = 0.89) and length ( r = 0.94 and 0.93), and were among the most reproducible as reflected by intraclass correlation coefficients (>0.98). The head circumference and chest circumference combination offered better goodness-of-fit and smaller limits of agreement than did either measure alone. The final model predicted weight within 10% and 15% of actual for 84% and 94% of infants, respectively, with no bias for postnatal age ( P = .76), gestational age ( P = .10), and sex ( P = .25). The model requires simple summation to generate a weight estimate and can be embodied as a low-cost, paper-based device