Determination of optimal vitamin D3 dosing regimens in HIV‐infected paediatric patients using a population pharmacokinetic approach

摘要

Aims To investigate 25-hydroxycholecalciferol [25(OH)D] population pharmacokinetics in children and adolescents, to establish factors that influence 25(OH)D pharmacokinetics and to assess different vitamin D₃ dosing schemes to reach sufficient 25(OH)D concentrations (>30?ng?ml?1). Methods This monocentric prospective study included 91 young HIV-infected patients aged 3 to 24 years. Patients received a 100?000 IU vitamin D₃ supplementation. A total of 171 25(OH)D concentrations were used to perform a population pharmacokinetic analysis. Results At baseline 28% of patients had 25(OH)D concentrations below 10?ng?ml?1, 69% between 10 and 30?ng?ml?1 and 3% above 30?ng?ml?1. 25(OH)D pharmacokinetics were best described by a one compartment model with an additional production parameter reflecting the input from diet and sun exposure. The effects of skin phototype and bodyweight were significant on 25(OH)D production before any supplementation. The basal level was 27% lower in non-white skin phototype patients and was slightly decreased with bodyweight. No significant differences in 25(OH)D concentrations were related to antiretroviral drugs. To obtain concentrations between 30 and 80?ng?ml?1, patients with baseline concentrations between 10 and 30?ng?ml?1 should receive 100?000 IU per 3 months. However, vitamin D deficient patients (?1) would need an intensive phase of 100?000 IU per 2 weeks (two times) followed 2 weeks later by a maintenance phase of 100?000 IU per 3 months. Conclusions Skin phototype and bodyweight had an influence on the basal production of 25(OH)D. According to 25(OH)D baseline concentrations, dosing schemes to reach sufficient concentrations are proposed.