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Model-Based Once-Daily Darunavir/Ritonavir Dosing Recommendations in Pediatric HIV-1-Infected Patients Aged ≥3 to <12 Years.

Brochot A, Kakuda TN, Van De Casteele T, Opsomer M, Tomaka FL, Vermeulen A, Vis P - CPT Pharmacometrics Syst Pharmacol (2015)

Bottom Line: The model was then used to provide once-daily dosing recommendations for darunavir/ritonavir in pediatric patients aged ≥3 to <12 years.The final model comprised two compartments with first-order absorption and apparent clearance dependent on the concentration of α1-acid glycoprotein.The recommended darunavir/ritonavir once-daily dosing regimens in children aged ≥3 to <12 years are: 35/7 mg/kg from 10 to <15 kg, 600/100 mg from 15 to <30 kg, 675/100 mg from 30 to <40 kg, and 800/100 mg for ≥40 kg.

View Article: PubMed Central - PubMed

Affiliation: Janssen Research & Development Beerse, Belgium.

ABSTRACT
An existing population pharmacokinetic model of darunavir in adults was updated using pediatric data from two studies evaluating weight-based, once-daily dosing of darunavir/ritonavir (ARIEL, NCT00919854 and DIONE, NCT00915655). The model was then used to provide once-daily dosing recommendations for darunavir/ritonavir in pediatric patients aged ≥3 to <12 years. The final model comprised two compartments with first-order absorption and apparent clearance dependent on the concentration of α1-acid glycoprotein. The recommended darunavir/ritonavir once-daily dosing regimens in children aged ≥3 to <12 years are: 35/7 mg/kg from 10 to <15 kg, 600/100 mg from 15 to <30 kg, 675/100 mg from 30 to <40 kg, and 800/100 mg for ≥40 kg. These doses should result in exposures similar to the adult exposure after treatment with darunavir/ritonavir 800/100 mg once daily, while minimizing pill burden and allowing a switch from suspension to tablet(s) as early as possible.

No MeSH data available.


Related in: MedlinePlus

Visual predictive checks of CL/F vs. (a) α1-acid glycoprotein concentration (AAG); (b) bodyweight; (c) total daily darunavir dose; and (d) age. The dots represent the observed parameters determined by a noncompartmental analysis, the black lines represent the 5th, 50th (median), and 95th percentile (with smoothing applied) of the parameters based on simulated values. Black dots represent adult DUET data, red dots DELPHI data, green dots ARIEL data, blue dots ARIEL QD substudy data, and pink dots DIONE data.
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fig03: Visual predictive checks of CL/F vs. (a) α1-acid glycoprotein concentration (AAG); (b) bodyweight; (c) total daily darunavir dose; and (d) age. The dots represent the observed parameters determined by a noncompartmental analysis, the black lines represent the 5th, 50th (median), and 95th percentile (with smoothing applied) of the parameters based on simulated values. Black dots represent adult DUET data, red dots DELPHI data, green dots ARIEL data, blue dots ARIEL QD substudy data, and pink dots DIONE data.

Mentions: The visual predictive checks of CL/F vs. all four covariates are shown in Figure3. The model performed well over the range of covariates of interest: AAG concentration, bodyweight, darunavir dose, and age. Furthermore, the parameter values obtained from noncompartmental analysis based on the simulated profiles agreed well with model input data.


Model-Based Once-Daily Darunavir/Ritonavir Dosing Recommendations in Pediatric HIV-1-Infected Patients Aged ≥3 to <12 Years.

Brochot A, Kakuda TN, Van De Casteele T, Opsomer M, Tomaka FL, Vermeulen A, Vis P - CPT Pharmacometrics Syst Pharmacol (2015)

Visual predictive checks of CL/F vs. (a) α1-acid glycoprotein concentration (AAG); (b) bodyweight; (c) total daily darunavir dose; and (d) age. The dots represent the observed parameters determined by a noncompartmental analysis, the black lines represent the 5th, 50th (median), and 95th percentile (with smoothing applied) of the parameters based on simulated values. Black dots represent adult DUET data, red dots DELPHI data, green dots ARIEL data, blue dots ARIEL QD substudy data, and pink dots DIONE data.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4544054&req=5

fig03: Visual predictive checks of CL/F vs. (a) α1-acid glycoprotein concentration (AAG); (b) bodyweight; (c) total daily darunavir dose; and (d) age. The dots represent the observed parameters determined by a noncompartmental analysis, the black lines represent the 5th, 50th (median), and 95th percentile (with smoothing applied) of the parameters based on simulated values. Black dots represent adult DUET data, red dots DELPHI data, green dots ARIEL data, blue dots ARIEL QD substudy data, and pink dots DIONE data.
Mentions: The visual predictive checks of CL/F vs. all four covariates are shown in Figure3. The model performed well over the range of covariates of interest: AAG concentration, bodyweight, darunavir dose, and age. Furthermore, the parameter values obtained from noncompartmental analysis based on the simulated profiles agreed well with model input data.

Bottom Line: The model was then used to provide once-daily dosing recommendations for darunavir/ritonavir in pediatric patients aged ≥3 to <12 years.The final model comprised two compartments with first-order absorption and apparent clearance dependent on the concentration of α1-acid glycoprotein.The recommended darunavir/ritonavir once-daily dosing regimens in children aged ≥3 to <12 years are: 35/7 mg/kg from 10 to <15 kg, 600/100 mg from 15 to <30 kg, 675/100 mg from 30 to <40 kg, and 800/100 mg for ≥40 kg.

View Article: PubMed Central - PubMed

Affiliation: Janssen Research & Development Beerse, Belgium.

ABSTRACT
An existing population pharmacokinetic model of darunavir in adults was updated using pediatric data from two studies evaluating weight-based, once-daily dosing of darunavir/ritonavir (ARIEL, NCT00919854 and DIONE, NCT00915655). The model was then used to provide once-daily dosing recommendations for darunavir/ritonavir in pediatric patients aged ≥3 to <12 years. The final model comprised two compartments with first-order absorption and apparent clearance dependent on the concentration of α1-acid glycoprotein. The recommended darunavir/ritonavir once-daily dosing regimens in children aged ≥3 to <12 years are: 35/7 mg/kg from 10 to <15 kg, 600/100 mg from 15 to <30 kg, 675/100 mg from 30 to <40 kg, and 800/100 mg for ≥40 kg. These doses should result in exposures similar to the adult exposure after treatment with darunavir/ritonavir 800/100 mg once daily, while minimizing pill burden and allowing a switch from suspension to tablet(s) as early as possible.

No MeSH data available.


Related in: MedlinePlus