Cisplatin protein binding in pregnancy and the neonatal period. 1994

D Zemlickis, and J Klein, and G Moselhy, and G Koren
Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada.

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.

UI MeSH Term Description Entries
D007231 Infant, Newborn An infant during the first 28 days after birth. Neonate,Newborns,Infants, Newborn,Neonates,Newborn,Newborn Infant,Newborn Infants
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D001798 Blood Proteins Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins. Blood Protein,Plasma Protein,Plasma Proteins,Serum Protein,Serum Proteins,Protein, Blood,Protein, Plasma,Protein, Serum,Proteins, Blood,Proteins, Plasma,Proteins, Serum
D002945 Cisplatin An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. Platinum Diamminodichloride,cis-Diamminedichloroplatinum(II),cis-Dichlorodiammineplatinum(II),Biocisplatinum,Dichlorodiammineplatinum,NSC-119875,Platidiam,Platino,Platinol,cis-Diamminedichloroplatinum,cis-Platinum,Diamminodichloride, Platinum,cis Diamminedichloroplatinum,cis Platinum
D005260 Female Females
D005312 Fetal Blood Blood of the fetus. Exchange of nutrients and waste between the fetal and maternal blood occurs via the PLACENTA. The cord blood is blood contained in the umbilical vessels (UMBILICAL CORD) at the time of delivery. Cord Blood,Umbilical Cord Blood,Blood, Cord,Blood, Fetal,Blood, Umbilical Cord,Bloods, Cord,Bloods, Fetal,Bloods, Umbilical Cord,Cord Blood, Umbilical,Cord Bloods,Cord Bloods, Umbilical,Fetal Bloods,Umbilical Cord Bloods
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D000704 Analysis of Variance A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable. ANOVA,Analysis, Variance,Variance Analysis,Analyses, Variance,Variance Analyses

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