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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

Expected darunavir exposures in children aged ≥3 to <18 years, weighing 10 to 65 kg at selected once-daily darunavir/ ritonavir regimens, given for the 5th, 50th (median), and 95th percentile of AAG concentrations, and compared to 80%, 100%, and 130% of the target exposure in adults (89.7 µg·h/ml, blue lines).
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fig04: Expected darunavir exposures in children aged ≥3 to <18 years, weighing 10 to 65 kg at selected once-daily darunavir/ ritonavir regimens, given for the 5th, 50th (median), and 95th percentile of AAG concentrations, and compared to 80%, 100%, and 130% of the target exposure in adults (89.7 µg·h/ml, blue lines).

Mentions: The expected darunavir exposures (AUCtau) are shown in Figure4 with darunavir once-daily dosing of: 35 mg/kg dose, 10 to 15 kg bodyweight; 600 mg dose, 15 to 30 kg bodyweight; 675 mg dose, 30 to 40 kg bodyweight; 800 mg dose, 40 to 65 kg. The expected exposures with darunavir/ritonavir once-daily dosing that most closely matched adult exposure, based on visual inspection of the plots, formed the basis for treatment recommendations. The mean exposures of the regimens shown in Figure4 are expected to be in the 80% to 130% range of the adult target (dosed with darunavir/ritonavir 800/100 mg once daily for average AAG concentrations). Simulation plots of all dosing strategies are shown in SupplementalFigure2.


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)

Expected darunavir exposures in children aged ≥3 to <18 years, weighing 10 to 65 kg at selected once-daily darunavir/ ritonavir regimens, given for the 5th, 50th (median), and 95th percentile of AAG concentrations, and compared to 80%, 100%, and 130% of the target exposure in adults (89.7 µg·h/ml, blue lines).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig04: Expected darunavir exposures in children aged ≥3 to <18 years, weighing 10 to 65 kg at selected once-daily darunavir/ ritonavir regimens, given for the 5th, 50th (median), and 95th percentile of AAG concentrations, and compared to 80%, 100%, and 130% of the target exposure in adults (89.7 µg·h/ml, blue lines).
Mentions: The expected darunavir exposures (AUCtau) are shown in Figure4 with darunavir once-daily dosing of: 35 mg/kg dose, 10 to 15 kg bodyweight; 600 mg dose, 15 to 30 kg bodyweight; 675 mg dose, 30 to 40 kg bodyweight; 800 mg dose, 40 to 65 kg. The expected exposures with darunavir/ritonavir once-daily dosing that most closely matched adult exposure, based on visual inspection of the plots, formed the basis for treatment recommendations. The mean exposures of the regimens shown in Figure4 are expected to be in the 80% to 130% range of the adult target (dosed with darunavir/ritonavir 800/100 mg once daily for average AAG concentrations). Simulation plots of all dosing strategies are shown in SupplementalFigure2.

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