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

• Published in: British journal of clinical pharmacology 2014-11, Vol.78 (5), p.1113-1121
• Main Authors: Foissac, Frantz, Meyzer, Candice, Frange, Pierre, Chappuy, Hélène, Benaboud, Sihem, Bouazza, Naïm, Friedlander, Gérard, Souberbielle, Jean‐Claude, Urien, Saïk, Blanche, Stéphane, Tréluyer, Jean‐Marc
• Format: Article
• Language: English
• Subjects: 25‐hydroxycholecalciferol; Adolescent; Bone Density Conservation Agents - administration & dosage; Bone Density Conservation Agents - blood; Bone Density Conservation Agents - pharmacokinetics; Bone Density Conservation Agents - therapeutic use; Child; children and adolescents; Cholecalciferol - administration & dosage; Cholecalciferol - blood; Cholecalciferol - pharmacokinetics; Cholecalciferol - therapeutic use; Dietary Supplements; Dose-Response Relationship, Drug; Female; HIV Infections - blood; HIV Infections - drug therapy; HIV Infections - virology; HIV-1 - isolation & purification; HIV‐infected patients; Humans; Male; Models, Biological; Paediatric Clinical Pharmacology; population pharmacokinetics; Precision Medicine; Prospective Studies; Viral Load; Vitamin D Deficiency - blood; Vitamin D Deficiency - drug therapy
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1111/bcp.12433

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 (