title: Determination of optimal vitamin D3 dosing regimens in HIV-infected paediatric patients using a population pharmacokinetic approach.
abstract: OBJECTIVE
  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.
authors.affiliation: EA 3620, Sorbonne Paris Cité, Université Paris Descartes, Paris, France; Unité de Recherche Clinique Paris Centre, Assistance Publique Hôpitaux de Paris (APHP), Paris, France.
authors.forename: Frantz
authors.initials: F
authors.lastname: Foissac
authors.forename: Candice
authors.initials: C
authors.lastname: Meyzer
authors.forename: Pierre
authors.initials: P
authors.lastname: Frange
authors.forename: Hélène
authors.initials: H
authors.lastname: Chappuy
authors.forename: Sihem
authors.initials: S
authors.lastname: Benaboud
authors.forename: Naïm
authors.initials: N
authors.lastname: Bouazza
authors.forename: Gérard
authors.initials: G
authors.lastname: Friedlander
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Souberbielle
authors.forename: Saïk
authors.initials: S
authors.lastname: Urien
authors.forename: Stéphane
authors.initials: S
authors.lastname: Blanche
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Tréluyer
mesh_terms: D000293:Adolescent; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002648:Child; D002762:Cholecalciferol / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008954:Models, Biological; D057285:Precision Medicine; D011446:Prospective Studies; D019562:Viral Load; D014808:Vitamin D Deficiency / Q000097:blood / Q000188:drug therapy*
chemical_list: D050071:Bone Density Conservation Agents; D002762:Cholecalciferol
keywords: 25-hydroxycholecalciferol; HIV-infected patients; children and adolescents; population pharmacokinetics