Placental transfer of the HIV integrase inhibitor dolutegravir in an ex vivo human cotyledon perfusion model.
J Antimicrob Chemother
; 71(2): 480-3, 2016 Feb.
Article
em En
| MEDLINE
| ID: mdl-26538508
ABSTRACT
OBJECTIVES:
Data on fetal exposure to antiretroviral agents during pregnancy are important to estimate their potential for prevention of mother-to-child transmission (PMTCT) and possible toxicity. For the recently developed HIV integrase inhibitor dolutegravir, clinical data on fetal disposition are not yet available. Dual perfusion of a single placental lobule (cotyledon) provides a useful ex vivo model to predict the in vivo maternal-to-fetal transfer of this drug. The aim of this study was to estimate the transfer of dolutegravir across the human term placenta, using a dual-perfusion cotyledon model.METHODS:
After cannulation of the cotyledons (n = 6), a fetal circulation of 6 mL/min and maternal circulation of 12 mL/min were initiated. The perfusion medium consisted of Krebs-Henseleit buffer (pH = 7.2-7.4) supplemented with 10.1 mM glucose, 30 g/L human serum albumin and 0.5 mL/L heparin 5000IE. Dolutegravir was administered to the maternal circulation (â¼ 4.2 mg/L) and analysed by UPLC-MS/MS.RESULTS:
After 3 h of perfusion, the mean ± SD fetal-to-maternal (FTM) concentration ratio of dolutegravir was 0.6 ± 0.2 and the mean ± SD concentrations in the maternal and fetal compartments were 2.3 ± 0.4 and 1.3 ± 0.3 mg/L, respectively.CONCLUSIONS:
Dolutegravir crosses the blood-placental barrier with a mean FTM concentration ratio of 0.6. Compared with other antiretroviral agents, placental transfer of dolutegravir is moderate to high. These data suggest that dolutegravir holds clinical potential for pre-exposure prophylaxis and consequently PMTCT, but also risk of fetal toxicity.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Placenta
/
Cotilédone
/
Inibidores de Integrase de HIV
/
Compostos Heterocíclicos com 3 Anéis
/
Modelos Biológicos
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
/
Pregnancy
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article