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

作者：Foissac Frantz^*; Meyzer Candice; Frange Pierre; Chappuy Helene; Benaboud Sihem; Bouazza Naim; Friedlander Gerard; Souberbielle Jean Claude; Urien Saik; Blanche Stephane; Treluyer Jean Marc

来源：British Journal of Clinical Pharmacology, 2014, 78(5): 1113-1121.

DOI：10.1111/bcp.12433

• 25-hydroxycholecalciferol
• children and adolescents
• HIV-infected patients
• population pharmacokinetics

AimsTo 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 (%26gt;30ngml(-1)). %26lt;br%26gt;MethodsThis monocentric prospective study included 91 young HIV-infected patients aged 3 to 24 years. Patients received a 100000 IU vitamin D-3 supplementation. A total of 171 25(OH)D concentrations were used to perform a population pharmacokinetic analysis. %26lt;br%26gt;ResultsAt baseline 28% of patients had 25(OH)D concentrations below 10ngml(-1), 69% between 10 and 30ngml(-1) and 3% above 30ngml(-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 80ngml(-1), patients with baseline concentrations between 10 and 30ngml(-1) should receive 100000 IU per 3 months. However, vitamin D deficient patients (%26lt;10ngml(-1)) would need an intensive phase of 100000 IU per 2 weeks (two times) followed 2 weeks later by a maintenance phase of 100000 IU per 3 months. %26lt;br%26gt;ConclusionsSkin 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.

• 出版日期2014-11