Contribution and limit of the model of perfused cotyledon to the study of placental transfer of drugs. Example of a protease inhibitor of HIV: Nelfinavir. European journal of obstetrics, gynecology, and reproductive biology [Eur J Obstet Gynecol Reprod Biol] Journal article | | Title | Contribution and limit of the model of perfused cotyledon to the study of placental transfer of drugs. Example of a protease inhibitor of HIV: Nelfinavir. | | Author(s) | Gavard L, Beghin D, Forestier F, Cayre Y, Peytavin G, Mandelbrot L, Farinotti R, Gil S | | Institution | Department of Clinical Pharmacy, University Paris-Sud 11, IFR141, School of Pharmacy, Châtenay-Malabry, France; Department of Obstetrics and Gynecology, AP-HP, Louis Mourier Hospital, University Denis Diderot Paris 7, Colombes, France. | | Source | Eur J Obstet Gynecol Reprod Biol 2009 Sep 19. | | Abstract | OBJECTIVES: The perfused cotyledon model is a very useful method to study placental transfer of drugs. Here we studied placental transfer of the human immunodeficiency virus protease inhibitor nelfinavir using the non-recirculating dual human placental perfusion with a main goal to determining the clearance index of nelfinavir as related to maternal concentrations, and analyze the conditions under which ex vivo and in vivo data can be correlated.
STUDY DESIGN: Thirteen human cotyledons, obtained after uneventful term pregnancies, were perfused in an open double circuit with nelfinavir (320-4436mug/l) and a freely diffusing marker antipyrine 20mg/l, in the presence of an albumin concentration of 2g/l. Drug concentrations were determined by high-performance liquid chromatography.
RESULTS: The mean clearance index of nelfinavir was very weak when maternal concentrations were under 500mug/l (0.03+/-0.05). For maternal concentrations above 1200mug/l, the mean fetal transfer rate was 14+/-3.4%, the mean clearance index was 0.39+/-0.10 and the fetal concentrations were between 133 and 671mug/l. There was a good correlation between maternal and fetal concentrations (r=0.86; p<0.001).
CONCLUSIONS: Our study with nelfinavir has achieved a good correlation between ex vivo and in vivo data. Our results also indicate that studies must be conducted under well defined conditions to obtain accurate and comparable data, underlining the fact that the ex vivo perfused cotyledon remains difficult to standardize as a model system. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19773109 |
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