AIMS: To investigate atazanavir (ATV) population pharmacokinetics in children and adolescents, establish factors that influence ATV pharmacokinetics and investigate the ATV exposure after recommended doses. METHODS: Atazanavir concentrations were measured in 51 children/adolescents during a mean therapeutic monitoring follow up of 6.6 months. A total of 151 ATV plasma concentrations were obtained, and a population pharmacokinetic model was developed with NONMEM. Patients received ATV alone or boosted with ritonavir. RESULTS: Atazanavir pharmacokinetics was best described by a one-compartment model with first-order absorption and elimination. The effect of bodyweight was added on both apparent elimination clearance (CL/F) and volume of distribution using allometric scaling. Atazanavir CL/F was reduced by ritonavir by 45%. Tenofovir disoproxil fumarate (TDF) co-medication (300 mg) increased significantly by 25% the atazanavir/ritonavir (ATV/r) CL/F. Mean ATV/r CL/F values with or without TDF were 8.9 and 7.1 L h(-1) (70 kg)(-1), respectively. With the recommended 250/100 mg and 300/100 mg ATV/r doses, the exposure was higher than the mean adult steady-state exposure in the bodyweight range of 32-50 kg. CONCLUSIONS: To target the mean adult exposure, children should receive the following once-daily ATV/r dose: 200/100 mg from 25 to 39 kg, 250/100 mg from 39 to 50 kg and 300/100 mg above 50 kg. When 300 mg TDF is co-administered, children should receive (ATV/r) at 250/100 mg between 35 and 39 kg, then 300/100 mg over 39 kg.
AIMS: To investigate atazanavir (ATV) population pharmacokinetics in children and adolescents, establish factors that influence ATV pharmacokinetics and investigate the ATV exposure after recommended doses. METHODS:Atazanavir concentrations were measured in 51 children/adolescents during a mean therapeutic monitoring follow up of 6.6 months. A total of 151 ATV plasma concentrations were obtained, and a population pharmacokinetic model was developed with NONMEM. Patients received ATV alone or boosted with ritonavir. RESULTS:Atazanavir pharmacokinetics was best described by a one-compartment model with first-order absorption and elimination. The effect of bodyweight was added on both apparent elimination clearance (CL/F) and volume of distribution using allometric scaling. Atazanavir CL/F was reduced by ritonavir by 45%. Tenofovir disoproxil fumarate (TDF) co-medication (300 mg) increased significantly by 25% the atazanavir/ritonavir (ATV/r) CL/F. Mean ATV/r CL/F values with or without TDF were 8.9 and 7.1 L h(-1) (70 kg)(-1), respectively. With the recommended 250/100 mg and 300/100 mg ATV/r doses, the exposure was higher than the mean adult steady-state exposure in the bodyweight range of 32-50 kg. CONCLUSIONS: To target the mean adult exposure, children should receive the following once-daily ATV/r dose: 200/100 mg from 25 to 39 kg, 250/100 mg from 39 to 50 kg and 300/100 mg above 50 kg. When 300 mg TDF is co-administered, children should receive (ATV/r) at 250/100 mg between 35 and 39 kg, then 300/100 mg over 39 kg.
Authors: R Giuntini; C Martinelli; E Ricci; F Vichi; E Gianelli; G Madeddu; C Abeli; L Palvarini; G Penco; P Marconi; C Grosso; G Pellicano; P Bonfanti; T Quirino Journal: HIV Med Date: 2009-08-03 Impact factor: 3.180
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