The maternal-fetal transfer of lamivudine in the ex vivo human placenta☆,☆☆,★
Section snippets
Material and methods
Term placentas were obtained from uncomplicated parturients undergoing elective cesarean deliveries in accordance with the guidelines set by the University of Texas Southwestern Medical Center Institutional Review Board. The placentas were transported to the laboratory in a saline solution within 10 minutes of delivery. The perfusion model used has been previously detailed.6, 7, 8 Briefly, a “fetal circulation” was reestablished by cannulating an artery and a vein on the fetal surface of a
Results
The clearance index of lamivudine at a maternal concentration of 1.39 μg/ml was 0.23 ± 0.14. At a peak maternal concentration of 14.68 μg/ml the clearance index was 0.14 ± 0.06. As illustrated in Table I, these clearance index values did not significantly change in the presence of 1 or 10 μg/ml of zidovudine (p = 0.9372). In addition, the concentration of lamivudine did not appear to influence its clearance index (p = 0.6224).
As also detailed in Table I, with multiple linear regression, the
Comment
The clearance index of lamivudine across the ex vivo human placenta does not appear to be affected by higher doses of lamivudine in the maternal circulation, suggesting a nonsaturable transport mechanism. Furthermore, the addition of zidovudine to the maternal perfusate did not affect the transfer of lamivudine. Our sample size precludes us from stating that there is absolutely no difference in the clearance index values between the two doses. Given our results, however, any difference
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2014, Reproductive ToxicologyCitation Excerpt :The human placental cotyledon model is an ex vivo model that is an established model for evaluation of potential fetal drug exposure. Bawdon and colleagues have analyzed multiple drugs such as bisheteroypiperazine, lamivudine, zidovudine, azidothymidine, 2′,3′-dideoxyinosine, 2′,3′-dideoxycytidine, and rosiglitazone and determined the amount that crossed the placental/trophoblastic barrier [22–28]. Low sample number and high variability within this model present limitations to this study.
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2014, American Journal of Obstetrics and GynecologyCitation Excerpt :The antipyrine assay was found to be linear over a concentration range of 6.25-100 μg/mL with a correlation coefficient (r) of 0.9981. In the literature placental perfusion studies have included 3 placentas evaluated at each concentration under both conditions of open/open and closed/closed models to determine descriptive statistical parameters such as mean values with SD and coefficient of variance.15-19 The low, middle, and high concentration transfer studies for carboplatin were each performed in 3 placentas for a total of 9 placentas that were included to complete the study.
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2012, Journal of Clinical and Experimental HepatologyCitation Excerpt :The 3% rate of congenital anomalies reported in this study also compares favorably to the 2.72% reported by the CDC birth defect surveillance system.74 In pregnant women, lamivudine crosses the placenta readily by simple diffusion.75 In a study of 57 HIV-infected pregnant women receiving lamivudine as part of antiretroviral therapy, maternal blood, cord blood and amniotic fluid samples correlated with fetal concentrations; and the median concentration in the amniotic fluid was 5 times higher than in maternal plasma.76
Antiretrovirals transfer across the human placenta
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From the Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center.
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Reprint requests: Steven L. Bloom, MD, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75235-9032.
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