Pharmacokinetic dynamic relationships
Vitamin D3 supplementation scheme in HIV-infected patients based upon pharmacokinetic modelling of 25-hydroxycholecalciferol
Mr Frantz Foissac, Unité de Recherche Clinique, Hôpital Tarnier, 89 rue d'Assas, F75006 Paris, France.
Tel.: +331 58 41 13 85
Fax: +331 58 41 11 83
Vitamin D deficiency is prevalent in HIV-infected patients and has been associated with osteopenia and HIV disease progression. Our aims were to investigate the pharmacokinetics of 25-hydroxycholecalciferol [25(OH)D], the effect of antiretroviral treatment (ARV) and others factors that may influence the pharmacokinetics, and to determine a vitamin D3 dosing scheme to reach the 30 ng ml−1 threshold (defined as 25(OH)D sufficiency).
This monocentric retrospective study included 422 HIV-infected patients aged 16 to 85 years. A total of 723 25(OH)D concentrations were available for pharmacokinetic evaluation and a population pharmacokinetic model was developed with MONOLIX 3.2.
Median 25(OH)D at baseline was 16 ng ml−1 (interquartile range 11–23 ng ml−1) for the total population, 17% of patient had concentrations below 10 ng ml−1, 68% between 10 and 30 ng ml−1 and 15% above 30 ng ml−1. 25(OH)D pharmacokinetics were best described by a one compartment model with an additional endogenous production. The effects of season and skin phototype were significant on production rate. The endogenous production was 20% lower in non-white skin phototype patients and was decreased by 16% during autumn, winter and spring. No significant differences in 25(OH)D concentrations were related to antiretroviral drugs (ARV). To obtain concentrations between 30 and 80 ng ml−1, the dosing recommendation was 100 000 IU every month.
Season and skin phototype had an influence on the endogenous production of 25(OH)D. However no effect of ARV was found. A dosing scheme to reach sufficient 25(OH)D concentrations is proposed.