Determination of optimal vitamin D 3 dosing regimens in HIV ‐infected paediatric patients using a population pharmacokinetic approach

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 D 3 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 D 3 supplementation. A total of 171 25( OH ) D concentrations were used to perform a population pharmacokinetic analysis. Results A t 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 (<10 ng ml −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.