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

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

Author information

1
Unité de Recherche Clinique, Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Tarnier, Paris, France.
2
EA7323, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
3
Unité d'Immunologie, Hématologie et Rhumatologie pédiatriques, AP-HP, Hôpital universitaire Necker - Enfants malades, Paris, France.
4
INSERM UMR1163, Institut Imagine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
5
Laboratoire de Microbiologie clinique, AP-HP, Hôpital Universitaire Necker - Enfants malades, Paris, France.
6
EA7328, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
7
Centre National de Référence Herpes Virus, Laboratoire associé, Paris, France.
8
Service de Pharmacologie clinique, AP-HP, Groupe hospitalier Paris Centre, Hôpital Cochin, Paris, France.
9
CIC-0901 INSERM, Cochin-Necker, Paris, France.
10
EA 7327, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.

Abstract

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.

PMID:
29860512
DOI:
10.1093/jac/dky192

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