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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.

During the 2009 H1N1 influenza pandemics, the concentrations of oseltamivir (O) and its active metabolite (oseltamivir carboxylate [OC]) were determined in 11 children (1 month to 16 years of age) admitted to intensive care units for presumed severe H1N1 infection. They received oseltamivir phosphate (OP) nasogastrically at doses between 1.5 and 6.8 mg/kg of body weight. High OC concentrations were found, with a mean level of 678 ± 535 μg/liter. The mean OP concentration was 27 ± 52 μg/liter. No marked side effect was reported.

The efficacy of drugs acting on lymphocytes like anticancer, immunosuppressive, and antiretroviral drugs depends on their intracellular concentrations, which could be modulated by membrane efflux pumps belonging to the ABC transporter superfamily. The gene expression profiles of 6 main ABC transporters (MDR1, MRP1, MRP3, MRP4, MRP5, and BCRP) were established in lymphocytes from birth to adulthood using blood samples from 57 children and 15 adults (34 and 5 HIV-infected, respectively). Gene expression levels were quantified by quantitative RT-PCR. In adults, the MRP1 gene had the highest expression, followed by the MRP5 gene. BCRP and MRP4 genes were significantly higher expressed at birth than after 1 month of life. Neither HIV infection nor antiretroviral therapies modulated the gene expression profiles of ABC transporters. In conclusion, drugs that are substrates of BCRP and MRP4, like zidovudine, may have an altered efficacy in newborns.