Cisplatin protein binding in pregnancy and the neonatal period.
The most effective combination regimes for ovarian cancer contain cisplatin, but there is little knowledge about cisplatin use during pregnancy. The high protein binding of cisplatin means that small changes in protein binding result in large changes in the fraction of free drug. It is the free form of cisplatin that crosses the placenta and may contribute to fetal toxicity. The purpose of the present study was to compare protein binding of cisplatin in pregnant women, non-pregnant women, and newborn infants. We found that babies and pregnant women had significantly lower concentrations of both protein and albumin compared to non-pregnant women. Analysis of variance found overall significant differences in protein binding among the three groups over time (P < .05). Babies had statistically less cisplatin protein binding than non-pregnant women at 80 minutes and all time points thereafter (P < .05). In contrast, pregnant women had statistically less cisplatin protein binding than non-pregnant women at 3.3 and 8 hours (P < .05). Of interest, at 75.2 hours, the percentage of free cisplatin was 15% in babies as compared with 9% in non-pregnant women and 10% in pregnant women. This means that the fetus is exposed to 50% higher platinum levels at equal total concentration. Cisplatin protein binding significantly correlated with albumin concentrations at 3.3, 8, and 24 hours (P < .01). Our analysis reveals that pregnancy and fetal changes in cisplatin protein binding are caused in large part by lower albumin levels. The resulting higher levels of free drug in the mother and fetus may increase the risk of toxicity in both.
Zemlickis
D
D
Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada.
Klein
J
J
Moselhy
G
G
Koren
G
G
D000328:Adult; D000704:Analysis of Variance; D001798:Blood Proteins / Q000493:pharmacokinetics*; D002945:Cisplatin / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn / Q000097:blood*; D011247:Pregnancy / Q000097:blood*; D011485:Protein Binding; D012709:Serum Albumin / Q000493:pharmacokinetics; D013997:Time Factors
D001798:Blood Proteins; D012709:Serum Albumin; D002945:Cisplatin