Model of population pharmacokinetics of cidofovir in immunocompromised children with cytomegalovirus and adenovirus infection

J Antimicrob Chemother. 2018 Sep 1;73(9):2422-2429. doi: 10.1093/jac/dky192.


Objectives: To describe cidofovir pharmacokinetics and assess the link between concentration and safety/efficacy in children.

Patients and methods: An observational study was conducted in 13 immunocompromised children receiving cidofovir for adenovirus and/or cytomegalovirus infection. A population pharmacokinetic model was built and AUC0-24 was derived for each patient. Virological success was defined as a decrease of the viraemia by ≥1 log10 copies/mL within 15 days of cidofovir initiation. The association between AUC0-24 and virological success was assessed using a Wilcoxon test. An AUC0-24 cut-off value was determined using a Fisher's exact test.

Results: Overall, 86 blood samples were analysed. A two-compartment model with first-order absorption and elimination best described the cidofovir data. Virological success (VS) was reached in 6/8 children with adenovirus viraemia and in 1/4 children with cytomegalovirus viraemia. Patients with VS displayed a non-significant higher median AUC0-24 compared with patients with virological failure: 48.6 (range 8.9-72.6) versus 19.1 (6.9-22.7) mg·h/L. Adenovirus-viraemic patients with an AUC0-24 value below 19.1 mg·h/L had a higher probability of treatment failure (P = 0.03). Aviraemic children with stool and/or nasopharyngeal adenovirus carriage cleared the viral carriage within a month of cidofovir initiation. During treatment, 1/13 children developed a tubulopathy but none of them had an increase in creatininaemia.

Conclusions: Cidofovir appears safe and reasonably well tolerated and seemed to have efficacy in a subset of patients with adenovirus/cytomegalovirus infection. Therapeutic drug monitoring may be useful in children receiving cidofovir and, in the case of adenovirus infection, targeting an AUC0-24 above 19.1 mg·h/L could be associated with higher probability of virological success.

Publication types

  • Observational Study

MeSH terms

  • Adenovirus Infections, Human / drug therapy*
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / adverse effects
  • Antiviral Agents / pharmacokinetics*
  • Antiviral Agents / pharmacology
  • Area Under Curve
  • Blood Chemical Analysis
  • Child
  • Child, Preschool
  • Cidofovir / administration & dosage
  • Cidofovir / adverse effects
  • Cidofovir / pharmacokinetics*
  • Cidofovir / pharmacology
  • Cytomegalovirus Infections / drug therapy*
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Female
  • Humans
  • Immunocompromised Host*
  • Infant
  • Male
  • Models, Statistical*
  • Treatment Outcome
  • Viral Load


  • Antiviral Agents
  • Cidofovir