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. 2014 Nov;78(5):1113-21.
doi: 10.1111/bcp.12433.

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

Frantz Foissac  1 , Candice Meyzer, Pierre Frange, Hélène Chappuy, Sihem Benaboud, Naïm Bouazza, Gérard Friedlander, Jean-Claude Souberbielle, Saïk Urien, Stéphane Blanche, Jean-Marc Tréluyer
Affiliations

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

Frantz Foissac et al. Br J Clin Pharmacol. 2014 Nov.

Abstract

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 (<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.

Keywords: 25-hydroxycholecalciferol; HIV-infected patients; children and adolescents; population pharmacokinetics.

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Figures

Figure 1
Figure 1
Prediction corrected visual predictive check for 25(OH)D concentrations vs. time. The lines show the 10th, 50th and 90th percentile of observed data. The areas represent the 90% confidence interval around the simulated percentiles
Figure 2
Figure 2
After 12 months of treatment, percentages of patients with 25(OH)D concentrations lower than 30 ng ml−1, between 30 and 80 ng ml−1 (target interval) and higher than 80 ng ml−1 (related to toxicity). formula image, <30 ng ml−1; formula image, 30–80 ng ml−1; formula image, >80 ng ml−1
Figure 3
Figure 3
Calculated 25(OH)D concentrations (solid line) and 90% CI (dashed lines) vs. time according to a 100 000 IU per 3 months dosing scheme in patients with baseline concentration <10 ng ml−1 (A), a 100 000 IU per 3 months dosing scheme in patients with baseline concentrations between 10 and 30 ng ml−1 (B) and an intensive (100 000 IU per 2 weeks, two times) and a maintenance dosing scheme (after 2 weeks, 100 000 IU per 3 months) in patients with baseline concentrations <10 ng ml−1 (C). The horizontal lines represent the 30 and 80 ng ml−1 25(OH)D targets for efficacy and toxicity, respectively
See this image and copyright information in PMC

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