An in-vivo study on placental transfer of naproxen in early human pregnancy.
BACKGROUND
Naproxen is one of the most common non-steroidal anti-inflammatory drugs used by women of reproductive age. Naproxen is known to be teratogenic in animals. The aim of this study was to investigate the placental transfer of naproxen in the first trimester of human pregnancy, and to determine the amount of the drug in different embryonic compartments.


METHODS
Twenty-eight patients who requested surgical termination of pregnancy in the first trimester were given two oral 500 mg doses of naproxen before the surgical procedure. Four biological samples, maternal venous blood, coelomic fluid, amniotic fluid and fetal tissue, were collected from each patient for drug analyses by high performance liquid chromatography.


RESULTS
Naproxen was detected in all samples. The mean (+/- SD) concentrations were 69.5 +/- 12.2 microg/ml, 6.4 +/- 2.4 microg/g, 1.85 +/- 1.03 microg/ml and 0.14 +/- 0.11 microg/ml in maternal serum, fetal tissue, coelomic fluid and amniotic fluid respectively. The mean amniotic fluid/maternal drug ratio and fetal/maternal drug ratio were 0.002 (range 0.0005-0.0064) and 0.092 (range 0.022-0.155) respectively. There was a positive correlation between the fetal drug concentration (r = 0.59, P = 0.001), amniotic fluid drug concentration (r = 0.47, P = 0.013), amniotic fluid/maternal ratio (r = 0.536, P = 0.003) and fetal/maternal ratio (r = 0.72, P < 0.001) with advancing gestational age.


CONCLUSIONS
Although naproxen can cross the placenta readily in the first trimester of human pregnancy, only a small amount was present in fetal tissues. Since there is no information on whether this small amount of naproxen would be teratogenic or not, women of reproductive age who are taking naproxen regularly should be warned of the possible fetal side-effects.
Siu
S S N
SS
Department of Obstetrics and Gynaecology, Prince of Wales Hospital, Shatin, Hong Kong. nelsonsiu@cuhk.edu.hk
Yeung
J H K
JH
Lau
T K
TK
D000653:Amniotic Fluid / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D005260:Female; D005333:Fetus / Q000378:metabolism; D006801:Humans; D009288:Naproxen / Q000493:pharmacokinetics*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy / Q000378:metabolism*; D013723:Teratogens / Q000493:pharmacokinetics*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013723:Teratogens; D009288:Naproxen