In:
British Journal of Clinical Pharmacology, Wiley, Vol. 78, No. 6 ( 2014-12), p. 1387-1396
Abstract:
The main goal of the study was to describe the pharmacokinetics of maternal zidovudine ( ZDV ) administration during pregnancy and labour and to evaluate their impact on fetal concentrations and exposures. Methods A total of 195 HIV ‐infected pregnant and non‐pregnant women aged 16–59 years were included and 273 maternal and 79 cord blood ZDV concentrations were collected. A population pharmacokinetic model was developed to describe ZDV concentrations as a function of time in the mother and the fetus. Fetal exposures resulting from maternal oral administration and infusion were estimated and compared with therapeutic exposures (3–5 mg l −1 h) and to exposure providing higher risk of toxicity ( 〉 8.4 mg l −1 h). Different protocols for ZDV administration during labour were simulated. Results The median fetal exposure and the percentage of children with values above 8.4 mg l −1 h were 3.20 mg l −1 h and 0% after maternal oral administration, respectively, and 9.71 mg l −1 h and 51% after maternal infusion during labour. Two options were considered to reduce fetal exposure during labour: (i) maternal infusion rates could be 1 mg kg −1 h −1 during 1 h followed by 0.5 mg kg −1 h −1 and (ii) the mother could only take oral ZDV every 5 h from start of labour until delivery with her neonate having their first ZDV dose as soon as possible after birth. Conclusions Zidovudine exposures are very important during labour and during the first days of a neonate's life. Maternal ZDV dose should be reduced in addition to the neonate doses reduction already proposed.
Type of Medium:
Online Resource
ISSN:
0306-5251
,
1365-2125
DOI:
10.1111/bcp.2014.78.issue-6
Language:
English
Publisher:
Wiley
Publication Date:
2014
detail.hit.zdb_id:
1498142-7
SSG:
15,3
