Skip Navigation LinksHome > August 15, 2013 - Volume 63 - Issue 5 > High Exposure to Zidovudine During the First 2 Weeks of Life...
JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0b013e3182908c00
Basic and Translational Science

High Exposure to Zidovudine During the First 2 Weeks of Life and Concentration—Toxicity Relationships

Hirt, Déborah PharmD, PhD*,†,‡; Warszawski, Josiane MD, PhD§,‖,¶; Firtion, Ghislaine MD, PhD#; Giraud, Carole PharmD, PhD*,†,‡,**; Chappuy, Hélène MD, PhD*,**,††,‡‡; Lechenadec, Jérôme PhD§; Benaboud, Sihem PharmD*,**; Urien, Saïk MD, PhD*,†,**; Blanche, Stéphane MD, PhD**,§§; Tréluyer, Jean-Marc MD, PhD*,†,‡,**

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Abstract

Objectives: The aims of the study were in a large group of neonates to identify the relative effect of bodyweight, postnatal age, and gestational age on zidovudine (ZDV) pharmacokinetics; to link concentrations with lactate and hemoglobin levels; and to find the more appropriate neonatal ZDV dose.

Methods: In 484 neonates aged 3–30 days, born to HIV-infected mothers, 767 ZDV and 417 ZDV glucuronide concentrations were collected.

Results: Using a population approach, ZDV clearance per kilogram increased with postnatal age but not with gestational age. High neonatal exposures were found as follows: 14,025 ng/mL·h the first week and 6528 ng/mL·h the second week in comparison to 3000 ng/mL·h in adults. At month 1, median lactate level was 2.8 mmol/L (60%, ≥2.5 mmol/L) and median hemoglobin was 10.1 g/dL (90%, <12 g/dL). ZDV trough concentrations at first sampling (days 3–7) or at last sampling (day 20 ± 10) were significantly negatively correlated to hemoglobin at months 1, 3, and 6 (P < 0.02). ZDV maximal or trough concentrations at days 3–7 and at day 20 ± 10 were significantly positively correlated to lactate levels at months 3 and 6, respectively.

Conclusions: To obtain an exposure comparable to adults, which should reduce neonatal toxicity, doses should to be decreased during the first 2 weeks of life.

© 2013 by Lippincott Williams & Wilkins

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