Lamivudine accumulates in amniotic fluid

Last Updated: 2001-02-13 17:15:35 EST (Reuters Health) 

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WESTPORT, CT (Reuters Health) - Lamivudine, when administered to pregnant women for prevention of vertical HIV transmission, appears to accumulate to high concentrations in amniotic fluid. 
 
Dr Laurent Mandelbrot of the Service de Gynecologie-Obstetrique in Paris, France, and a multicenter team measured levels of lamivudine in amniotic fluid, maternal blood, and cord blood of 57 mother-infant pairs. "All women were infected with HIV type 1 and were receiving lamivudine at the time of delivery," they write in the January issue of the American Journal of Obstetrics and Gynecology. 
 
Maternal and fetal concentrations of lamivudine were strongly correlated, with a median ratio of approximately 1. This ratio implies
that the drug freely crosses the placenta via diffusion, the authors note. At a median 8.5 hours after the last maternal lamivudine dose of
150 ng/mL, maternal and fetal plasma levels of the drug were 302 ng/mL and 240 ng/mL, respectively. 
 
While the median concentration of lamivudine in amniotic fluid was 5 times higher than in maternal plasma, the ratio ranged to as high as
133. "The ratio of the amniotic fluid concentration to the maternal plasma concentration tended to increase with the time elapsed since the last maternal dose," Dr Mandelbrot and colleagues say, "which suggests that accumulation of the compound occurs in the amniotic fluid compartment." 
 
While such high concentrations of lamivudine in amniotic fluid may have benefits in terms of postexposure prophylaxis against vertical HIV transmission, there is concern about mucosal toxicity of this drug in infants. The authors recommend that neonates exposed to lamivudine in utero "should be carefully examined, with particular attention paid to the eyes, larynx, pharynx, and tongue." 
 
Am J Obstet Gynecol. 2001;184:153-158.