Pharmacy World and Science

, Volume 20, Issue 4, pp 139–148 | Cite as

Mechanisms of drug transfer across the human placenta.

  • Eric M. van der Aa
  • Jenny H.J. Copius Peereboom-Stegeman
  • Jan Noordhoek
  • Frank W.J. Gribnau
  • Frans G.M. Russel


In this review we summarized literature data on the mechanisms of human placental drug transport studied in the isolated perfused placental cotyledon, placental membrane vesicles or trophoblastic cell cultures. Overall human placental drug transport rarely exceeds the transfer of flow‐dependent and membrane‐limited marker compounds. Interestingly, relatively often placental drug transfer appeared to be much smaller, indicating impaired trans-placental transport, depending on the physico-chemical characteristics of the drug or placental factors such as tissue binding or metabolism. Although in perfusion studies overall human placental drug transport occurs by simple diffusion, at the membrane level several drug transport systems have been found, mainly for drugs structurally related to endogenous compounds.

Human placenta Drug transfer Drug transport Pharmacokinetics Placenta perfusion Membrane vesicles Cotyledon Trophoblast Cell culture 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Page KR. The physiology of the human placenta. England: Kings Lynn and Guilford Biddles Ltd, 1993.Google Scholar
  2. 2.
    Schneider H. Placental transport function. Reprod Fert Dev 1991;3:345-53.Google Scholar
  3. 3.
    Mihaly GW and Morgan DJ. Placental drug transfer: effects of gestational age and species. Pharmacol Ther 1984;23:253-66.Google Scholar
  4. 4.
    Murray MA. The bundle of life 1930. Ancient Egypt III:65-73.Google Scholar
  5. 5.
    Seligmann CG and Murray MA. Note upon an early Egyptian standard 1911. Man 11 no 97:165-71.Google Scholar
  6. 6.
    Mossmann HW. Comparative morphogenesis of the fetal membranes and accessory uterine structures Contrib Embryol 1937;26:129-246.Google Scholar
  7. 7.
    Amoroso EC. Histology of the placenta. Brit Med Bull 1961;17:1-95.Google Scholar
  8. 8.
    Grosser O. Vergleichende Anatomie und Entwicklungsgeschichte der Eihäute und der Placenta. Vienna: Braumuller, 1909.Google Scholar
  9. 9.
    Christensen HN and Streicher JA. Association between rapid growth and elevated cell concentrations of amino acids in fetal tisues. J Biol Chem 1948;175:95-100.Google Scholar
  10. 10.
    Faber JJ and Thornburg KL. Placental physiology-structure and function of fetomaternal exchange. New York: Raven Press, 1983.Google Scholar
  11. 11.
    Sibley CP and Boyd CAR. Mechanisms of transfer across the human placenta in fetal and neonatal physiology. Philadelphia: Saunders, 1992.Google Scholar
  12. 12.
    Netter FH. The Ciba collection of medical illustrions, vol 2 Reproductive System, 1965.Google Scholar
  13. 13.
    Schneider H. The role of the placenta in nutrition of the human fetus. Am J Obstet Gynecol 1991;164:967-73.PubMedGoogle Scholar
  14. 14.
    Boyd RDH, Haworth C, Stacey TE and Ward RHT. Permeability of the sheep placenta to unmetabolized polar non electrolytes. J Physiol 1976;256:617-34.PubMedGoogle Scholar
  15. 15.
    Schneider H, Sodha RJ, Prögler M and Young MPA. Permeability of the human placent for hydrophylic substances studied in the isolated dually in vitro perfused lobe. Contrib Gynecol Obstet 1985;13:98-103.PubMedGoogle Scholar
  16. 16.
    Bain MD, Copas DK, Landon MJ and Stacey TE. In vivo permeability of the human placenta to inulin and mannitol. J Physiol 1988;399:313-9.PubMedGoogle Scholar
  17. 17.
    Willis DM, O'Grady JP, Faber JJ and Thornburg KL. Diffusion permeability of cyanocobalamine in human placenta. Am J Physiol 1986;250:R459-R464.PubMedGoogle Scholar
  18. 18.
    Thornburg KL, Burry KJ, Adams AK, Kirk EP and Faber JJ. Permeability of the placenta to inulin. Am J Obstet Gynecol 1988;158:1165-9.PubMedGoogle Scholar
  19. 19.
    Jansson T, Powell TL and Illsley NP. Non-electrolyte solute permeabilities of human placental microvillous and basal membranes. J Physiol 1993;468:261-74.PubMedGoogle Scholar
  20. 20.
    Stulc J. Validity of the equivalent pores model in placental physiology. Contrib Gynecol Obstet 1985;13:85-91.PubMedGoogle Scholar
  21. 21.
    Kaufmann P, Schroeder H, Leichtweiss H-P and Winterhager E. Are there membrane-lined channels through the trophoblast? A study with lanthanum hydroxide. Troph Res 1987;2:557-71.Google Scholar
  22. 22.
    Thornburg KL and Faber JJ. Transfer of hydrophylic molecules by placenta and yolk-sac of the guinea pig. Am J Physiol 1977;33:C111-C124.Google Scholar
  23. 23.
    Fox H. A contemporary view of the human placenta. Midwifery 1991;7:31-9.PubMedGoogle Scholar
  24. 24.
    Boyd JD and Hamilton WH. Development and structure of the human placenta from the end of the 3rd month of gestation. J Obstet Gynecol Brit Common 1967;74:161-226.Google Scholar
  25. 25.
    Bonati M, Bortolus R, Marchetti F, Romero M and Tognoni G. Drug use in pregnancy: an overview of epidemiological (drug utilization) studies. Eur J Clin Pharmacol 1990;38:325-8.PubMedGoogle Scholar
  26. 26.
    De Jong-van den Berg LTW, Van den Berg PB, Haaijer-Ruskamp FM, Dukes MNG and Wesseling H. Investigating drug use in pregnancy-methodological problems and perspectives. Pharm Weekbl Sci Ed 1991;13:32-8.Google Scholar
  27. 27.
    Ramamoorthy S, Leibach FH, Mahesh VB and Ganapathy V. Selective impairment of taurine transport by cyclosporin A in a human placental cell line. Ped Res 1992;32:125-7.Google Scholar
  28. 28.
    Shennan DB and Russell TVN. Salicylate inhibits human placental sulphate transport in vitro. Biochem Pharmacol 1991;41:723-8.PubMedGoogle Scholar
  29. 29.
    Balkovetz DF, Miyamoto Y, Tiruppathi C, Mahesh VB Leibach FH and Ganapathy V. Inhibition of brush-border membrane Na+/H+-exchanger by loperamide. J Pharmacol Exp Ther 1987;243:150-5.PubMedGoogle Scholar
  30. 30.
    Ganapathy ME, Leibach FH, Mahesh VB, Devoe LD and Ganapathy V. Interaction of clonidine with human placental Na+/H+-exchanger. Biochem Pharmacol 1986;35:3989-94.PubMedGoogle Scholar
  31. 31.
    Ganapathy V, Balkovetz DF, Miyamoto Y, Ganapathy ME, Mahesh VB, Devoe LD and Leibach FH. Inhibition of human placental Na+/H+-exchanger by cimetidine. J Pharmacology Exp Ther 1986;239:192-7.Google Scholar
  32. 32.
    Prasad PD, Leibach FH, Mahesh VB and Ganapathy V. Specific interaction of 5-(N-methyl-N-isobutyl)amiloride with the organic cation-proton antiporter in human placental brush-border membrane vesicles. J Biol Chem 1992;267:23632-9.PubMedGoogle Scholar
  33. 33.
    Ganapathy V, Ganapathy ME, Nair CN, Mahesh VB and Leibach FH. Evidence for an organic cation-proton antiport system in brush-border membranes isolated from the human term placenta. J Biol Chem 1988; 263:4561-8.PubMedGoogle Scholar
  34. 34.
    Waddell WJ and Marlowe C. Transfer of drugs across the placenta. Pharmacol Ther 1981;14:375-90.PubMedGoogle Scholar
  35. 35.
    Levy G. Pharmacokinetics of fetal and neonatal exposure to drugs. Obstet Gynecol 1981;58:9S-16S.PubMedGoogle Scholar
  36. 36.
    Chamberlain G. Placental transfer of drugs. Clin Exp Obstet Gynecol 1986; 8:107-12.Google Scholar
  37. 37.
    Simone C, Derewlany LO and Koren G. Drug transfer across the placenta, considerations in treatment and research. Fet Drug Ther 1994;21:463-81.Google Scholar
  38. 38.
    Cole DE. Sulphate transport in brush-border membrane vesicles prepared from human placental syncytiotrophoblast. Biochim and Biophys Res Com 1984;123:223-9.Google Scholar
  39. 39.
    Brunette MG and Allard S. Phosphate uptake by syncytial brush-border membranes of human placenta. Ped Res 1985;19:1179-82.Google Scholar
  40. 40.
    Shennan DB, Davis B and Boyd CAR. Chloride transport in human placental microvillus membrane vesicles, evidence for anion exchange. Pflüg Arch 1986;406:60-4.Google Scholar
  41. 41.
    Byrne S, Glazier JD, Greenwood SL, Mahendran D and Sibley C. Chloride transport by human placental microvillous membrane vesicles. Biochim Biophys Acta 1993;1153:122-6.PubMedGoogle Scholar
  42. 42.
    Balkovetz DF, Leibach FH, Mahesh VB and Ganapathy V. A proton gradient is the driving force for uphill transport of lactate in human placental brush-border membrane vesicles. J Biol Chem 1988;263:13823-30.PubMedGoogle Scholar
  43. 43.
    Ganapathy V, Ganapathy ME, Tiruppathi C, Miyamoto Y, Mahesh VB and Leibach FH. Sodium-gradient-driven, high affinity, uphill transport of succinate in human placental brush-border membrane vesicles. Biochem J 1988;249:179-84.PubMedGoogle Scholar
  44. 44.
    Balkovetz DF, Leibach FH, Mahesh VB, Devoe LD, Cragoe Jr. J and Ganapathy V. Na+/H+-exchanger of human placental brush-border membrane: identification and characterization. Am J Physiol 1986;251:C852-C860.PubMedGoogle Scholar
  45. 45.
    Faller DP, O'Reilly CM and Ryan MP. Amiloride sensitive sodium uptake into human placental brush-border membrane vesicles. Biochem Pharmacol 1994;47:757-61.PubMedGoogle Scholar
  46. 46.
    Simon BJ, Kulanthaivel P, Burkhardt G, Ramamoorthy S, Leibach FH and Ganapathy V. Characterization of an ATP driven H+ pump in human placental brush-border membrane vesicles. Biochem J 1992;287:423-30.PubMedGoogle Scholar
  47. 47.
    Fisher GJ, Kelley LK and Smith CH ATP-dependent calcium transport across basal plasma membranes of human placental trophoblast. Am J Physiol 1987;21:C38-C46.Google Scholar
  48. 48.
    Brunette MG and Leclerc M. Ca+ transport through the brush border membrane of human placenta syncytiotrophoblasts. Can J Physiol Pharmacol 1991;70:835-42.Google Scholar
  49. 49.
    van der Aa EM, Wouterse AC, Copius Peereboom-Stegeman JHJ and Russel FGM. Uptake of choline into syncytial microvillus membrane vesicles of human term placenta. Biochem Pharmacol 1994;47:453-6.PubMedGoogle Scholar
  50. 50.
    Grassl SM. Choline transport in human placental brush-border membrane vesicles. Biochim Biophys Acta 1994;1194:203-13.PubMedGoogle Scholar
  51. 51.
    Yudilevich DL and Sweiry JH. Transport of amino acids in the placenta. Biochim Biophys Acta 1985;822:169-201.PubMedGoogle Scholar
  52. 52.
    Johnson LW and Smith CH. Monosaccharide transport across microvillous membrane of human placenta. Am J Physiol 1980;38:C160-C168.Google Scholar
  53. 53.
    Johnson LW and Smith CH. Glucose transport across the basal plasma membrane of human placental syncytiotrophoblast. Biochim Biophys Acta 1985;815:44-50.PubMedGoogle Scholar
  54. 54.
    Ganapathy ME, Mahesh VB, Devoe LD, Leibach FH and Ganapathy V. Dipeptide transport in brush-border membrane vesicles isolated from normal term human placenta. Am Obstet Gynecol 1985;153:83-6.Google Scholar
  55. 55.
    Dumaswala R, Setchell KDR, Moyer MS and Suchy FJ. An anion exchanger mediates bile acid transport across the placental microvillous membrane. Am J Physiol 1993;264:G1016-G1023.PubMedGoogle Scholar
  56. 56.
    Marin JJ, Serrano MA, El-Mir MY, Eleno N and Boyd CAR. Bile acid transport by basal membrane vesicles of human term placental trophoblast. Gastroenterol 1990;99:1431-8.Google Scholar
  57. 57.
    Shennan DB and Boyd CAR. Ion transport by the placenta: a review of membrane transport systems. Biochim Biophys Acta 1987;906:437-57.PubMedGoogle Scholar
  58. 58.
    Kulanthaivel P, Furesz TC, Moe AJ, Smith CH, Mahesh VB, Leibach FH and Ganapathy V. Human placental syncytiotrophoblast expresses two pharmacologically distinguishable types of Na+/H+-exchangers, NHE-1 in the maternal facing (brush-border) membrane and NHE-2 in the fetal facing (basal) membrane. Biochem J 1992;284:33-8.PubMedGoogle Scholar
  59. 59.
    Kulanthaivel P, Leibach FH, Mahesh VB, Cragoe EJ Jr. and Ganapathy V. The Na+/H+-exchanger of the placental brush-border membrane is pharmacologically distinct from that of the renal brush-border membrane. J Biol Chem 1990;265:1249-52.PubMedGoogle Scholar
  60. 60.
    Schneider H, Panigel M and Dancis J. Transfer across the perfused human placenta of antipyrine, sodium and leucine. Am J Obstet Gynecol 1972;114:822-8.PubMedGoogle Scholar
  61. 61.
    Murer H and Kinne R. The use of isolated membrane vesicles to study epithelial transport processes. J Memb Biol 1980;55:81-95.Google Scholar
  62. 62.
    Wachter I, Weissenbacher ER, Schulze K and Sörgel F. Study to compare ceftriaxone with cefotetane and cefotaxime in a human placental perfusion model. International J Exp Clin Chemother 1992;5:149-51.Google Scholar
  63. 63.
    Fortunato SJ, Roger MD, Bawdon E and Baum M. Placental transfer of cefoperazone and sulbactam in the isolated in vitro perfused human placenta. Am J Obstet Gynecol 1988;159:1002-6.PubMedGoogle Scholar
  64. 64.
    Fortunato SJ, Roger MD, Maberry MC and Swan KF. Transfer of ceftizoxime surpasses that of cefoperazone by the isolated human placenta perfused in vitro. Obstet Gynecol 1990;75:830-3.PubMedGoogle Scholar
  65. 65.
    Giroux M, Dumas JC, Lenfant B, Navarret N, Grandlean H and Houin G. Placental transfer of cefpodoxime and cefotaxime: an ex vivo study. Eur J Drug Metab Parmacokin 1993;18:P161.Google Scholar
  66. 66.
    Closse C, Saux MC, Breilh D, Bouvier d' Yvoire M, Grellet J and Leng JJ. Penetration placentaire du cefpirone (HR180): étude des concentrations foetales apres perfusion in vitro de placenta humane a terme. Pathol Biol 1994;42:297-304.PubMedGoogle Scholar
  67. 67.
    Kudo Y, Urabe T, Fujiwara A, Yamada K and Kawasaki T. Carrier-mediated transport system for cephalexin in human placental brush-border membrane vesicles. Biochim Biophys Acta 1989;978:313-8.PubMedGoogle Scholar
  68. 68.
    Akbaraly JP, Guibert S, Leng JJ and Auzerie J. Etude du passage transplacentaire de cinq antibiotiques par perfusion in vitro du placenta humain. Pathol Biol 1985;33:368-72.PubMedGoogle Scholar
  69. 69.
    Bawdon RE, Maberry MC, Fortunato SJ, Gilstrap LC and Kim S. Trimethoprim and sulfamethoxazole transfer in the in vitro perfused human cotyledon. Gynecol Obstet Invest 1991;31:240-2.PubMedGoogle Scholar
  70. 70.
    Onur MA, Kirby CJ, Isimer A, Beksac S, Bacsi N, Pamir R, Coskun T and Tumer A. Effect of liposomal encapsulation of chloramphenicol on its transfer across the human placenta in a dual in vitro perfusion system. Int J Pharm 1992;88:313-7.Google Scholar
  71. 71.
    Fortunato SJ and Bawdon RE. Determination of pentamidine transfer in the in vitro perfused human cotyledon with highperformance liquid chromatography. Am J Obstet Gynecol 1989;160:759-61.PubMedGoogle Scholar
  72. 72.
    Fortunato SJ, Bawdon RE, Swan KF, Bryant EC and Sobhi S. Transfer of timetin (ticarcillin and clavulanic acid) across the in vitro perfused human placenta: comparison with other agents. Am J Obstet Gynecol 1992;167:1595-9.PubMedGoogle Scholar
  73. 73.
    Quetin CF, Besnard RM, Bonnard X, Akbaraly R, Brachet-Liebermain A, Leng JJ and Bebear C. Étude préliminaire in vitro du passage transplacentaire de la spiramycine. Pathol Biol 1983;31:425-8.PubMedGoogle Scholar
  74. 74.
    Jacobson RL, Brewer A, Eis A, Siddiqi TA and Myat L. Transfer of aspirin across the perfused human placental cotyledon. Am J Obstet Gynecol 1991;165:939-44.PubMedGoogle Scholar
  75. 75.
    Wiegand UW, Chou RC, Muulik D and Levy G. Assessment of biotransformation during transfer of propoxyphene and acetaminophen across the isolated perfused human placenta. Ped Pharmacol 1984;4:145-53.Google Scholar
  76. 76.
    Akbaraly R, Leng JJ, Brachet-Liermain A, White P and Laclau-Lacrouts B. Passage trans-placentaire de quatre anti-inflammatoires-son étude par perfusion in vitro. J Gynecol Obstet Biol Rep 1981;10:7-11.Google Scholar
  77. 77.
    Kluck RM, Cannell GR, Hooper WD, Eadie MJ and Dickinson RG. Disposition of pheytoin and phenobarbitone in the isolated perfused human placenta. Clin Exp Pharmacol Physiol 1988;15:827-36.PubMedGoogle Scholar
  78. 78.
    Shah YG and Miller RK. The pharmacokinetics of phenytoin in perfused human placenta. Ped Pharmacol 1985;5:165-79.Google Scholar
  79. 79.
    Dickinson RG, Fowler DW and Kluck RM. Maternofetal transfer of phenytoin, p-hydroxy-phenytoin and p-hydroxyphenytoin-glucuronide in the perfused human placenta. Clin Exp Pharmacol Physiol 1989;16:789-97.PubMedGoogle Scholar
  80. 80.
    Pienimaki P, Hartikainen AL, Arvela P, Partanen T, Herva R, Pelkonen O and Vahakangas K. Carbamazepine and its metabolites in human perfused placenta and in maternal and cord blood. Epilepsia 1995;36:241-8.PubMedGoogle Scholar
  81. 81.
    Fowler DW, Eadie MJ and Dickinson RG. Transplacental transfer and biotransformation studies of valproic acid and its gluceronides in the perfused human placenta. J Pharmacol Exp Ther 1989;249:318-23.PubMedGoogle Scholar
  82. 82.
    Bawdon RE, Sobhi S and Dax J The transfer of anti-human immunodeficiency virus nucleoside compounds by the term placenta. Am J Obstet Gynecol 1992;167:1570-4.PubMedGoogle Scholar
  83. 83.
    Schenker S, Johnson RF, King TS, Schenken RS and Henderson GI. Azidothymidine (Zidovudine) transport by the human placenta. Am J Med Sci 1990;299:16-20.PubMedGoogle Scholar
  84. 84.
    Liebes L, Mendoza S, Wilson D and Dancis J. Transfer of zidovudine (AZT) by human placenta. J Infec Dis 1990;161:203-7.Google Scholar
  85. 85.
    Liebes L, Mendoza S, Lee JD and Dancis J. Further observations on zidovudine transfer and metabolism by human placenta. AIDS 1993;7:590-1.PubMedGoogle Scholar
  86. 86.
    Qian M, Bui T, Ho RJY and Unadkat JD. Metabolism of 3′-azido-3′-deoxythymidine (AZT) in human placental trophoblasts and Hofbauer cells. Biochem Pharmacol 1994;48:383-9.PubMedGoogle Scholar
  87. 87.
    Dancis J, Lee JD, Mendoza S and Liebes L. Transfer and metabolism of dideoxyinosine by the perfused human placenta. J Acq Imm Def Syn 1993;6:2-6.Google Scholar
  88. 88.
    Henderson GI, Perez AB, Yang Y, Hamby RL, Schenken RS and Schenker S. Transfer of dideoxyinosine across the human isolated placenta. Brit J Clin Pharmacol 1994;38:237-42.Google Scholar
  89. 89.
    Dalton JT and Au JL-S. 2′,3′-dideoxyinosine is not metabolized in human placenta. Drug Metab Disp 1993;21:544-6.Google Scholar
  90. 90.
    Bawdon RE, Kaul S and Sobhi S. The ex vivo transfer of the anti-HIV nucleoside compound d4T in the human placenta. Gynecol Obstet Invest 1994;38:1-4.PubMedGoogle Scholar
  91. 91.
    Henderson GI, Hu Z-Q, Johnson RF, Perez AB, Yang Y and Schenker S. Acyclovir transport by the human placenta. J Lab Clin Med 1992;120:885-92.PubMedGoogle Scholar
  92. 92.
    Henderson GI, Hu Z-Q, Yang Y, Perez TB, Devi BG, Frosto TA and Schenker S. Ganciclovir transfer by the human placenta and its effect on rat fetal cells. Am J Med Sci 1993;306:151-6.PubMedGoogle Scholar
  93. 93.
    Gilstrap LC, Bawdon RE, Roberts SW and Sobhi S. The transfer of the nucleoside analog ganciclovir across the perfused human placenta. Am J Obstet Gynecol 1994;170:967-73.PubMedGoogle Scholar
  94. 94.
    Roberts S, Bawdon RE, Sobhi S, Dax J, Gilstrap L and Wimberly D. The maternal-fetal transfer of bisheterooypiperazine in the ex vivo human placenta. Am J Obstet Gynecol 1995;172:88-91.PubMedGoogle Scholar
  95. 95.
    Schneider H and Proegler M. Placental transfer of ß-adrenergic antagonists studied in an in vitro perfusion system of human placental tissue. Am J Obstet Gynecol 1988;159:42-7.PubMedGoogle Scholar
  96. 96.
    Urbach J, Mor L, Fuchs S and Brandes JM. Transplacental transfer of ritodrine and its effect on placental glucose and oxygen consumption in an in vitro human placental cotyledon perfusion. Gynecol Obstet Invest 1991;32:10-4.PubMedGoogle Scholar
  97. 97.
    Nandakumaran M, Gardey CL, Rey E, Challier J-C, Panigel M and Olive G. Transfer of ritodrine and norepinephrine in human placenta: in vitro study. Dev Pharmacol Ther 1982;4:71-80.PubMedGoogle Scholar
  98. 98.
    Sodha RJ and Schneider H. Transplacental transfer of betaadrenergic drugs studied by an in vitro perfusion method of an isolated human placental lobule. Am J Obstet Gynecol 1983;147:303-10.PubMedGoogle Scholar
  99. 99.
    Nandakumaran M, Gardey CL, Challier J-C, Richard M-O, Panigel M and Olive G. Transfer of salbutamol in the human placenta in vitro. Dev Pharmacol Ther 1981;3:88-98.PubMedGoogle Scholar
  100. 100.
    Derewlany LO, Leeder JS, Kumar R, Radde IC, Knie B and Koren G. The transport of digoxin across the perfused human placental lobule. J Pharmacol Exp Ther 1991;256:1107-11.PubMedGoogle Scholar
  101. 101.
    Schenker S, Yang Y, Johnson RF, Downing JW, Schenken RS, Henderson GI and King TS. The transfer of cocaine and its metabolites across the term human placenta. Clin Pharmacol Ther 1993;53:329-39.PubMedGoogle Scholar
  102. 102.
    Krishna RB, Levitz M and Dancis J. Transfer of cocaine by the perfused human placenta: the effect of binding to serum proteins. Am J Obstet Gynecol 1993;169:1418-23.PubMedGoogle Scholar
  103. 103.
    Simone C, Derewlany LO, Oskamp M, Knie B and Koren G. Transfer of cocaine and benzecgonine across the perfused human placental cotyledon. J Obstet Gynecol 1994;170:1404-10.Google Scholar
  104. 104.
    Fant ME, Harbison RD and Harrison RW. Glucocorticoid uptake into human placental membrane vesicles. J Biol Chem 1979;254:6218-21.PubMedGoogle Scholar
  105. 105.
    Fant ME, Yeakley J and Harrison RW. Evidence for carriermediated transport of glucocorticoids by human placental membrane vesicles. Biochim Biophys Acta 1983;731:415-29.PubMedGoogle Scholar
  106. 106.
    Smith MA, Thomford PJ, Mattison DR and Slikker Jr. W. Transport and metabolism of dexamethasone in the dually perfused human placenta. Reprod Toxicol 1988;2:37-43.PubMedGoogle Scholar
  107. 107.
    Addison RS, Maguire DJ, Mortimer RH and Cannell GR. Metabolism of prednisolone by the isolated perfused human placental lobule. J Ster Biochem Mol Biol 1991;39:83-90.Google Scholar
  108. 108.
    Addison RS, Maguire DJ, Mortimer RH, Roberts MS and Cannell GR. Pathway and kinetics of prednisolone metabolism in the human placenta. J Ster Biochem Mol Biol 1993;44:315-20.Google Scholar
  109. 109.
    Levitz M, Jansen V and Dancis J. The transfer and metabolism of corticosteroids in the perfused human placenta. Am J Obstet Gynecol 1978;132:363-6.PubMedGoogle Scholar
  110. 110.
    Elliott BD, Langer O, Schenker S and Johnson RF. Insignificant transfer of glyburide occurs across the human placenta. Am J Obstet Gynecol 1991;165:807-12.PubMedGoogle Scholar
  111. 111.
    Ching MS, Czuba MA, Mihaly GW, Morgan DJ, Hyman KM, Paull JD and Smallwood RA. Mechanism of triamterene transfer across the human placenta. J Pharmacol Exp Ther 1988;246:1093-7.PubMedGoogle Scholar
  112. 112.
    Omarini D, Barzago MM, Bortolotti A, Lucchini G, Stellari F, Efrati S and Bonati M. Placental transfer of theophylline in an in vitro closed perfusion system of human placenta isolated lobule. Eur J Drug Metab Pharmacokin 1993;18:369-74.Google Scholar
  113. 113.
    Omarini D, Barzago MM, Aramayona J, Bortolotti A, Lucchini G and Bonati M. Theophylline transfer across human placental cotyledon during in vitro dual perfusion. J Med 1992;23:101-16.PubMedGoogle Scholar
  114. 114.
    Schenker S, Dicke J, Johnson RF, Mor LL and Henderson GI. Human placental transport of cimetidine. J Clin Invest 1987;80:1428-1434.PubMedGoogle Scholar
  115. 115.
    Ching MS, Mihaly GW, Morgan DJ, Date NM, Hardy KJ and Smallwood RA. Low clearance of cimetidine across the human placenta. J Pharmacol Exp Ther 1987;241:1006-9.PubMedGoogle Scholar
  116. 116.
    Dicke JM, Johnson RF, Henderson GI, Kuehl TJ and Schenker S. A comparative evaluation of the transport of H2-receptor antagonists by the human and baboon placenta. Am J Med Sci 1988;295:198-206.PubMedGoogle Scholar
  117. 117.
    Guerre-Millo M, Rey E, Challier J-C, Turquais J-M, d'Athis Ph and Olive G. Transfer in vitro of three benzodiazepines across the human placenta. Eur J Clin Pharmacol 1979;15:171-3.PubMedGoogle Scholar
  118. 118.
    Guerre-Millo M, Challier J-C, Rey E, Nandakumaran M, Richard MO and Olive G. Maternofetal transfer of two benzodiazepines; effect of plasma protein binding and placental uptake. Dev Pharmacol Ther 1982;4:158-72.PubMedGoogle Scholar
  119. 119.
    Nandakumaran M, Challier J-C, Rey E, Richard MO and Olive G. In vitro transfer of six benzamides in the human placenta. Dev Pharmacol Ther 1984;7 sup 1:60-6.PubMedGoogle Scholar
  120. 120.
    Johnson RF, Herman N, Arney TL, Gonzalez H, Johnson HV and Downing JW. Bupivacaine transfer across the human term placenta: a study using the dual perfused human placental model. Anesthesiology 1995;2:459-68.Google Scholar
  121. 121.
    Zakowski MI, Ham AA and Grant GJ. Transfer and uptake of alfentanil in the human placenta during in vitro perfusion. Anesth Analges 1994;79:1089-93.Google Scholar
  122. 122.
    Bajoria R and Contractor SF. Transfer of heparin across the human perfused placental lobule. J Pharm Pharmacol 1992;44:952-9.PubMedGoogle Scholar
  123. 123.
    Barzago MM, Omarini D, Bortolotti A, Stellari FF, Lucchini G, Efrati S and Bonati M. Mefloquine transfer during in vitro human placental perfusion. J Pharmacol Exp Ther 1994;269:28-31.PubMedGoogle Scholar
  124. 124.
    Leng JJ, Mbanzulu PN, Akbaraly JP, Albin H, Guibert S, Gravier J and Demotes-Mainard F. Etude in vitro du passage trans-placentaire du sulfate de chloroquine. Pathol Biol 1987;35:1051-4.PubMedGoogle Scholar
  125. 125.
    Walenga RW, Kuhn DC and Stuart MJ. Trans-placental transport and metabolism of carbacyclin by perfused human placental in vitro. Prostaglandins 1989;37:121-34.PubMedGoogle Scholar
  126. 126.
    Kuhn DC, Walenga RW and Stuart MJ. A prostacyclin analogue crosses the in vitro perfused human placenta and improves transfer in some pathologic states. Am J Perinatol 1991;8:179-84.PubMedGoogle Scholar
  127. 127.
    Ghabrial H, Czuba MA, Stead CK, Smallwood RA and Morgan DJ. Transfer of acipimox across the isolated perfused human placenta. Placenta 1991;12:653-61.PubMedGoogle Scholar
  128. 128.
    Nandakumaran M and Eldeen AS. Transfer of cyclosporine in the perfused human placenta. Dev Pharmacol Ther 1990;15:101-5.PubMedGoogle Scholar
  129. 129.
    Derewlany LO, Knie B and Koren G. Human placental transfer and metabolism of p-aminobenzoic acid. J Pharmacol Exp Ther 1994;69:761-5.Google Scholar
  130. 130.
    Juchau MR. Drug biotransformation in the placenta. Pharmacol Ther 1980;8:501-24.PubMedGoogle Scholar
  131. 131.
    Ramamoorthy S, Leibach FH, Mahesh VB and Ganapathy V. Active transport of dopamine in human placental brush-border membrane vesicles. Am J Physiol 1992;262:C1189-C1196.PubMedGoogle Scholar
  132. 132.
    Ramamoorthy S, Prasad PD, Kulanthaivel P, Leibach FH, Blakely RD and Ganapathy V. Expression of a cocaine-sensitive norepinephrine transporter in the human placental syncytiotrophoblast. Biochemistry 1993;32:1346-53.Google Scholar
  133. 133.
    Balkovetz DF, Tiruppathi C, Leibach FH, Mahesh VB and Ganapathy V. Evidence for an imipramine-sensitive serotonin transporter in human placental brush-border membranes. J Biol Chem 1989;264:2195-8.PubMedGoogle Scholar
  134. 134.
    Cool DR, Leibach FH and Ganapathy V. Interaction of fluoxetine with the human placental serotonin transporter. Biochem Pharmacol 1990;40:2161-7.PubMedGoogle Scholar
  135. 135.
    Cool DR, Leibach FH, and Ganapathy V. High-affinity paroxetine binding to the human placental serotonin transporter. Am J Physiol 1990;59:C196-C204.Google Scholar
  136. 136.
    Dancis J, Levitz M, Katz J, Wilson D, Blaner WS, Piantedosi R and Goodman DS. Transfer and metabolism of retinol by the perfused human placenta. Ped Res 1992;32:195-9.Google Scholar
  137. 137.
    Green T and Ford HC. Human placental microvilli contain high-affinity binding sites for folate. Biochem J 1984;218:75-80.PubMedGoogle Scholar
  138. 138.
    Habibzadeh N, Green M, Schorah CJ and Levene MI. Methyl-folate transport by human placental microvilli vesicles associated with neural tube defects. J Physiol 1994;475:90P.Google Scholar
  139. 139.
    Bissonette JM, Weiner CP and Power Jr. GG. Amino acid uptake and chloride conductances in human placenta. Placenta 1994;15:445-6, lett.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1998

Authors and Affiliations

  • Eric M. van der Aa
    • 1
  • Jenny H.J. Copius Peereboom-Stegeman
    • 1
  • Jan Noordhoek
    • 1
  • Frank W.J. Gribnau
    • 1
  • Frans G.M. Russel
    • 1
  1. 1.Departments of Pharmacology and Toxicology, Faculty of Medical SciencesUniversity of NijmegenNijmegenThe Netherlands

Personalised recommendations