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Journal of Biomedicine and Biotechnology
Volume 2011 (2011), Article ID 783528, 13 pages
http://dx.doi.org/10.1155/2011/783528
Review Article

Clinical Therapeutics in Pregnancy

1Department of Obstetrics and Gynecology, Washington Hospital Center, Washington, DC 20010, USA
2Eunice Kennedy Shriver National Institute of Child Health and Human Development , NIH, Bethesda, MD 10892, USA

Received 22 October 2010; Accepted 3 May 2011

Academic Editor: Farhad Kamali

Copyright © 2011 Maisa N. Feghali and Donald R. Mattison. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. R. A. Black and D. A. Hill, “Over-the-counter medications in pregnancy,” American Family Physician, vol. 67, no. 12, pp. 2517–2524, 2003. View at Scopus
  2. E. H. Riley, E. Fuentes-Afflick, R. A. Jackson et al., “Correlates of prescription drug use during pregnancy,” Journal of Women's Health, vol. 14, no. 5, pp. 401–409, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  3. M. Bonati, R. Bortolus, F. Marchetti, M. Romero, and G. Tognoni, “Drug use in pregnancy: an overview of epidemiological (drug utilization) studies,” European Journal of Clinical Pharmacology, vol. 38, no. 4, pp. 325–328, 1990. View at Scopus
  4. W. F. Rayburn and K. C. Farmer, “Off-label prescribing during pregnancy,” Obstetrics and Gynecology Clinics of North America, vol. 24, no. 3, pp. 471–478, 1997. View at Publisher · View at Google Scholar · View at Scopus
  5. W. F. Rayburn, “A physician's prerogative to prescribe drugs for off-label uses during pregnancy,” Obstetrics and Gynecology, vol. 81, no. 6, pp. 1052–1055, 1993. View at Scopus
  6. G. D. Anderson, “Pregnancy-induced changes in pharmacokinetics: a mechanistic-based approach,” Clinical Pharmacokinetics, vol. 44, no. 10, pp. 989–1008, 2005. View at Publisher · View at Google Scholar · View at Scopus
  7. N. Papantoniou, G. Ismailos, G. Daskalakis et al., “Pharmacokinetics of oral cefatrizine in pregnant and non-pregnant women with reference to fetal distribution,” Fetal Diagnosis and Therapy, vol. 22, no. 2, pp. 100–106, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  8. C. C. Hill and J. Pickinpaugh, “Physiologic changes in pregnancy,” Surgical Clinics of North America, vol. 88, no. 2, pp. 391–401, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  9. A. Malek and R. Leiser, “Influence of the magnesium aspartate hydrochloride administration to the maternal circuit on the aspartate concentration of the fetal circuit under in vitro perfusion of human placenta,” European Journal of Obstetrics Gynecology and Reproductive Biology, vol. 142, no. 1, pp. 12–17, 2009. View at Publisher · View at Google Scholar · View at PubMed
  10. S. V. Kane and L. A. Acquah, “Placental transport of immunoglobulins: a clinical review for gastroenterologists who prescribe therapeutic monoclonal antibodies to women during conception and pregnancy,” American Journal of Gastroenterology, vol. 104, no. 1, pp. 228–233, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  11. A. L. H. J. Aarnoudse, J. P. Dieleman, and B. H. C. Stricker, “Age- and gender-specific incidence of hospitalisation for digoxin intoxication,” Drug Safety, vol. 30, no. 5, pp. 431–436, 2007. View at Publisher · View at Google Scholar · View at Scopus
  12. D. R. Mattison, “Environmental exposures and development,” Current Opinion in Pediatrics, vol. 22, no. 2, pp. 208–218, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  13. R. G. Abellar, J. R. Pepperell, D. Greco et al., “Effects of chemotherapy during pregnancy on the placenta,” Pediatric and Developmental Pathology, vol. 12, no. 1, pp. 35–41, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  14. S. Ravindran, O. L. Zharikova, R. A. Hill, T. N. Nanovskaya, G. D. V. Hankins, and M. S. Ahmed, “Identification of glyburide metabolites formed by hepatic and placental microsomes of humans and baboons,” Biochemical Pharmacology, vol. 72, no. 12, pp. 1730–1737, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  15. G. D. Anderson, “Sex differences in drug metabolism: cytochrome P-450 and uridine diphosphate glucuronosyltransferase,” Journal of Gender-Specific Medicine, vol. 5, no. 1, pp. 25–33, 2002. View at Scopus
  16. J. K. Chun, M. Piquette-Miller, L. Zhang, and K. M. Giacomini, “Expression of human polyspecific renal organic cation transport activity in Xenopus laevis oocytes,” Journal of Pharmaceutical Sciences, vol. 86, no. 6, pp. 753–755, 1997. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  17. FDA, Health Organizations to Study Safety of Medications Taken During Pregnancy, FDA News Release 2009, http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2009/ucm195934.htm.
  18. E. R. Yeomans and L. C. Gilstrap, “Physiologic changes in pregnancy and their impact on critical care,” Critical Care Medicine, vol. 33, no. 10, supplement, pp. S256–S258, 2005. View at Publisher · View at Google Scholar
  19. S. L. Clark, D. B. Cotton, W. Lee, et al., “Central hemodynamic assessment of normal term pregnancy,” American Journal of Obstetrics and Gynecology, vol. 161, no. 6, part 1, pp. 1439–1442, 1989.
  20. J. J. Bonica and J. S. McDonald, Principles and Practice of Obstetric Analgesia and Anesthesia, Williams & Wilkins, Baltimore, Md, USA, 2nd edition, 1995.
  21. A. Nakai, I. Sekiya, A. Oya, T. Koshino, and T. Araki, “Assessment of the hepatic arterial and portal venous blood flows during pregnancy with Doppler ultrasonography,” Archives of Gynecology and Obstetrics, vol. 266, no. 1, pp. 25–29, 2002. View at Publisher · View at Google Scholar
  22. J. J. Duvekot, E. C. Cheriex, F. A. A. Pieters, P. P. C. A. Memheere, and L. L. H. Peeters, “Early pregnancy changes in hemodynamics and volume homeostasis are consecutive adjustments triggered by a primary fall in systemic vascular tone,” American Journal of Obstetrics and Gynecology, vol. 169, no. 6, pp. 1382–1392, 1993.
  23. J. P. Granger, “Maternal and fetal adaptations during pregnancy: lessons in regulatory and integrative physiology,” American Journal of Physiology, Regulatory Integrative and Comparative Physiology, vol. 283, no. 6, pp. R1289–R1292, 2002.
  24. F. E. Hytten, The Physiology of Human Pregnancy, Vlack-Well, Oxford, UK, 2nd edition, 1971.
  25. S. TE, “Placental transfer,” in Clinical Physiology in Obstetrics, G. Chamberlain and F. Hytten, Eds., p. 419, Blackwell Scientific Publications, Oxford, UK, 1991.
  26. S. A. Qasqas, C. McPherson, W. H. Frishman, and U. Elkayam, “Cardiovascular pharmacotherapeutic considerations during pregnancy and lactation,” Cardiology in Review, vol. 12, no. 4, pp. 201–221, 2004. View at Publisher · View at Google Scholar · View at PubMed
  27. B. B. K. Pirani, D. M. Campbell, and I. MacGillivray, “Plasma volume in normal first pregnancy,” The Journal of Obstetrics and Gynaecology of the British Commonwealth, vol. 80, no. 10, pp. 884–887, 1973.
  28. M. D. Lindheimer, S. J. Taler, and F. G. Cunningham, “ASH position paper: hypertension in pregnancy,” Journal of Clinical Hypertension, vol. 11, no. 4, pp. 214–225, 2009. View at Publisher · View at Google Scholar · View at PubMed
  29. B. M. Sibai, “Treatment of hypertension in pregnant women,” The New England Journal of Medicine, vol. 335, no. 4, pp. 257–265, 1996. View at Publisher · View at Google Scholar · View at PubMed
  30. B. M. Sibai and C. L. Stella, “Diagnosis and management of atypical preeclampsia-eclampsia,” American Journal of Obstetrics and Gynecology, vol. 200, no. 5, pp. 481.e1–481.e7, 2009. View at Publisher · View at Google Scholar · View at PubMed
  31. S. McCoy and K. Baldwin, “Pharmacotherapeutic options for the treatment of preeclampsia,” American Journal of Health-System Pharmacy, vol. 66, no. 4, pp. 337–344, 2009. View at Publisher · View at Google Scholar · View at PubMed
  32. J. M. Roberts and C. A. Hubel, “The two stage model of preeclampsia: variations on the theme,” Placenta, vol. 30, supplement, pp. 32–37, 2009. View at Publisher · View at Google Scholar · View at PubMed
  33. R. M. Smiley and M. Finster, “Do receptors get pregnant too? adrenergic receptor alterations in human pregnancy,” Journal of Maternal-Fetal and Neonatal Medicine, vol. 5, no. 3, pp. 106–114, 1996.
  34. S. Hogstedt and A. Rane, “Plasma concentration—effect relationship of metoprolol during and after pregnancy,” European Journal of Clinical Pharmacology, vol. 44, no. 3, pp. 243–246, 1993.
  35. S. Hogstedt, B. Lindberg, and Dun Reng Peng, “Pregnancy-induced increase in metoprolol metabolism,” Clinical Pharmacology and Therapeutics, vol. 37, no. 6, pp. 688–692, 1985.
  36. M. F. Hebert, D. B. Carr, G. D. Anderson et al., “Pharmacokinetics and pharmacodynamics of atenolol during pregnancy and postpartum,” Journal of Clinical Pharmacology, vol. 45, no. 1, pp. 25–33, 2005. View at Publisher · View at Google Scholar · View at PubMed
  37. A. Philipson, “Pharmacokinetics of antibiotics in pregnancy and labour,” Clinical Pharmacokinetics, vol. 4, no. 4, pp. 297–309, 1979.
  38. M. A. Andrew, T. R. Easterling, D. B. Carr et al., “Amoxicillin pharmacokinetics in pregnant women: modeling and simulations of dosage strategies,” Clinical Pharmacology and Therapeutics, vol. 81, no. 4, pp. 547–556, 2007. View at Publisher · View at Google Scholar · View at PubMed
  39. A. Philipson and G. Stiernstedt, “Pharmacokinetics of cefuroxime in pregnancy,” American Journal of Obstetrics and Gynecology, vol. 142, no. 7, pp. 823–828, 1982.
  40. M. Mirochnick, J. H. Rodman, B. L. Robbins et al., “Pharmacokinetics of oral zidovudine administered during labour: a preliminary study,” HIV Medicine, vol. 8, no. 7, pp. 451–456, 2007. View at Publisher · View at Google Scholar · View at PubMed
  41. J. Moodley, “Pharmacokinetics and antiretroviral activity of lamivudine alone or when coadministered with zidovudine in human immunodeficiency virus type 1-infected pregnant women and their offspring,” Journal of Infectious Diseases, vol. 178, no. 5, pp. 1327–1333, 1998.
  42. A. M. Stek, M. Mirochnick, E. Capparelli et al., “Reduced lopinavir exposure during pregnancy,” AIDS, vol. 20, no. 15, pp. 1931–1939, 2006. View at Publisher · View at Google Scholar · View at PubMed
  43. B. W. Kosel, K. P. Beckerman, S. Hayashi, M. Homma, and F. T. Aweeka, “Pharmacokinetics of nelfinavir and indinavir in HIV-1-infected pregnant women,” AIDS, vol. 17, no. 8, pp. 1195–1199, 2003. View at Publisher · View at Google Scholar
  44. M. F. Hebert, X. Ma, S. B. Naraharisetti et al., “Are we optimizing gestational diabetes treatment with glyburide the pharmacologic basis for better clinical practice,” Clinical Pharmacology and Therapeutics, vol. 85, no. 6, pp. 607–614, 2009. View at Publisher · View at Google Scholar · View at PubMed
  45. A. M. E. Luxford and G. S. M. Kellaway, “Pharmacokinetics of digoxin in pregnancy,” European Journal of Clinical Pharmacology, vol. 25, no. 1, pp. 117–121, 1983.
  46. M. F. Hebert, T. R. Easterling, B. Kirby et al., “Effects of pregnancy on CYP3A and P-glycoprotein activities as measured by disposition of midazolam and digoxin: a University of Washington Specialized Center of Research Study,” Clinical Pharmacology and Therapeutics, vol. 84, no. 2, pp. 248–253, 2008. View at Publisher · View at Google Scholar · View at PubMed
  47. G. J. De Haan, P. Edelbroek, J. Segers et al., “Gestation-induced changes in lamotrigine pharmacokinetics: a monotherapy study,” Neurology, vol. 63, no. 3, pp. 571–573, 2004.
  48. R. Knutti, H. Rothweiler, and C. Schlatter, “Effect of pregnancy on the pharmacokinetics of caffeine,” European Journal of Clinical Pharmacology, vol. 21, no. 2, pp. 121–126, 1981.
  49. J. C. Gluck, “The change of asthma course during pregnancy,” Clinical Reviews in Allergy and Immunology, vol. 26, no. 3, pp. 171–180, 2004. View at Publisher · View at Google Scholar · View at PubMed
  50. K. G. Barnette, M. A. Sarkar, D. D. Glover, P. Li, C. Boyd, and D. Lalka, “Glutathione S-transferase in human endometrium: quantitation and interindividual variability in isoform content,” Gynecologic and Obstetric Investigation, vol. 47, no. 2, pp. 114–119, 1999. View at Publisher · View at Google Scholar
  51. D. D. Glover and B. Larsen, “Relationship of fungal vaginitis therapy to prior antibiotic exposure,” Infectious Disease in Obstetrics and Gynecology, vol. 11, no. 3, pp. 157–160, 2003. View at Publisher · View at Google Scholar · View at PubMed
  52. M. P. Dombrowski, M. Schatz, R. Wise et al., “Asthma during pregnancy,” Obstetrics and Gynecology, vol. 103, no. 1, pp. 5–12, 2004. View at Publisher · View at Google Scholar · View at PubMed
  53. K. Chambers, “Asthma education and outcomes for women of childbearing age,” Case Manager, vol. 14, no. 6, pp. 58–61, 2003. View at Publisher · View at Google Scholar
  54. V. E. Murphy, P. Gibson, P. I. Talbot, and V. L. Clifton, “Severe asthma exacerbations during pregnancy,” Obstetrics and Gynecology, vol. 106, no. 5, part 1, pp. 1046–1054, 2005.
  55. M. Schatz, R. S. Zeiger, K. Harden, C. C. Huffman, L. Chilingar, and D. Petitti, “The safety of asthma and allergy medications during pregnancy,” Journal of Allergy and Clinical Immunology, vol. 100, no. 3, pp. 301–306, 1997. View at Publisher · View at Google Scholar
  56. M. Schatz, M. P. Dombrowski, R. Wise et al., “The relationship of asthma medication use to perinatal outcomes,” Journal of Allergy and Clinical Immunology, vol. 113, no. 6, pp. 1040–1045, 2004. View at Publisher · View at Google Scholar · View at PubMed
  57. M. T. V. Chan, P. Mainland, and T. Gin, “Minimum alveolar concentration of halothane and enflurane are decreased in early pregnancy,” Anesthesiology, vol. 85, no. 4, pp. 782–786, 1996. View at Publisher · View at Google Scholar
  58. I. Kawabata, A. Nakai, and T. Takeshita, “Prediction of HELLP syndrome with assessment of maternal dual hepatic blood supply by using Doppler ultrasound,” Archives of Gynecology and Obstetrics, vol. 274, no. 5, pp. 303–309, 2006. View at Publisher · View at Google Scholar · View at PubMed
  59. C. K. Cheung, T. Lao, and R. Swaminathan, “Urinary excretion of some proteins and enzymes during normal pregnancy,” Clinical Chemistry, vol. 35, no. 9, pp. 1978–1980, 1989.
  60. A. Erman, A. Neri, R. Sharoni et al., “Enhanced urinary albumin excretion after 35 weeks of gestation and during labour in normal pregnancy,” Scandinavian Journal of Clinical and Laboratory Investigation, vol. 52, no. 5, pp. 409–413, 1992.
  61. M. Hayashi, Y. Ueda, K. Hoshimoto et al., “Changes in urinary excretion of six biochemical parameters in normotensive pregnancy and preeclampsia,” American Journal of Kidney Diseases, vol. 39, no. 2, pp. 392–400, 2002.
  62. M. D. Hill and F. P. Abramson, “The significance of plasma protein binding on the fetal/maternal distribution of drugs at steady-state,” Clinical Pharmacokinetics, vol. 14, no. 3, pp. 156–170, 1988.
  63. S. Sudhakaran, C. R. Rayner, J. Li, D. C. M. Kong, N. M. Gude, and R. L. Nation, “Differential protein binding of indinavir and saquinavir in matched maternal and umbilical cord plasma,” British Journal of Clinical Pharmacology, vol. 63, no. 3, pp. 315–321, 2007. View at Publisher · View at Google Scholar · View at PubMed
  64. S. Sudhakaran, C. R. Rayner, J. Li, D. C. M. Kong, N. M. Gude, and R. L. Nation, “Inhibition of placental P-glycoprotein: impact on indinavir transfer to the foetus,” British Journal of Clinical Pharmacology, vol. 65, no. 5, pp. 667–673, 2008. View at Publisher · View at Google Scholar · View at PubMed
  65. A. Ayrton and P. Morgan, “Role of transport proteins in drug discovery and development: a pharmaceutical perspective,” Xenobiotica, vol. 38, no. 7-8, pp. 676–708, 2008. View at Publisher · View at Google Scholar · View at PubMed
  66. A. Malek and D. R. Mattison, “Drug development for use during pregnancy: impact of the placenta,” Expert Review of Obstetrics and Gynecology, vol. 5, no. 4, pp. 437–454, 2010. View at Publisher · View at Google Scholar
  67. J. Behravan and M. Piquette-Miller, “Drug transport across the placenta, role of the ABC drug efflux transporters,” Expert Opinion on Drug Metabolism and Toxicology, vol. 3, no. 6, pp. 819–830, 2007. View at Publisher · View at Google Scholar · View at PubMed
  68. A. Haimeur, G. Conseil, R. G. Deeley, and S. P. C. Cole, “The MRP-related and BCRP/ABCG2 multidrug resistance proteins: biology, substrate specificity and regulation,” Current Drug Metabolism, vol. 5, no. 1, pp. 21–53, 2004. View at Publisher · View at Google Scholar
  69. C. Gedeon and G. Koren, “Designing pregnancy centered medications: drugs which do not cross the human placenta,” Placenta, vol. 27, no. 8, pp. 861–868, 2006. View at Publisher · View at Google Scholar · View at PubMed
  70. J. M. Davison, “The effect of pregnancy on kidney function in renal allograft recipients,” Kidney International, vol. 27, no. 1, pp. 74–79, 1985.
  71. M. D. Lindheimer, J. M. Davison, and A. I. Katz, “The kidney and hypertension in pregnancy: twenty exciting years,” Seminars in Nephrology, vol. 21, no. 2, pp. 173–189, 2001.
  72. E. R. Yeomans and L. C. Gilstrap, “Physiologic changes in pregnancy and their impact on critical care,” Critical Care Medicine, vol. 33, no. 10, supplement, pp. S256–S258, 2005. View at Publisher · View at Google Scholar
  73. M. Schou, A. Amdisen, and O. R. Steenstrup, “Lithium and pregnancy: II. Hazards to women given lithium during pregnancy and delivery,” British Medical Journal, vol. 2, no. 5859, pp. 137–138, 1973.
  74. M. R. Syme, J. W. Paxton, and J. A. Keelan, “Drug transfer and metabolism by the human placenta,” Clinical Pharmacokinetics, vol. 43, no. 8, pp. 487–514, 2004. View at Publisher · View at Google Scholar
  75. M. V. St.-Pierre, M. A. Serrano, R. I. R. Macias et al., “Expression of members of the multidrug resistance protein family in human term placenta,” American Journal of Physiology, Regulatory Integrative and Comparative Physiology, vol. 279, no. 4, pp. R1495–R1503, 2000.
  76. M. Tanabe, I. Ieiri, N. Nagata et al., “Expression of P-glycoprotein in human placenta: relation to genetic polymorphism of the multidrug resistance (MDR)-1 gene,” Journal of Pharmacology and Experimental Therapeutics, vol. 297, no. 3, pp. 1137–1143, 2001.
  77. S. Hoffmeyer, O. Burk, O. Von Richter et al., “Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 7, pp. 3473–3478, 2000.
  78. J. H. Wang, D. A. Scollard, S. Teng, R. M. Reilly, and M. Piquette-Miller, “Detection of P-glycoprotein activity in endotoxemic rats by 99mTc-sestamibi imaging,” Journal of Nuclear Medicine, vol. 46, no. 9, pp. 1537–1545, 2005.
  79. Y. H. Chen, J. P. Wang, H. Wang et al., “Lipopolysaccharide treatment downregulates the expression of the pregnane X receptor, cyp3a11 and mdr1a genes in mouse placenta,” Toxicology, vol. 211, no. 3, pp. 242–252, 2005. View at Publisher · View at Google Scholar · View at PubMed
  80. P. Myllynen, E. Immonen, M. Kummu, and K. Vähäkangas, “Developmental expression of drug metabolizing enzymes and transporter proteins in human placenta and fetal tissues,” Expert Opinion on Drug Metabolism and Toxicology, vol. 5, no. 12, pp. 1483–1499, 2009. View at Publisher · View at Google Scholar · View at PubMed
  81. A. Gulati and P. M. Gerk, “Role of placental ATP-binding cassette (ABC) transporters in antiretroviral therapy during pregnancy,” Journal of Pharmaceutical Sciences, vol. 98, no. 7, pp. 2317–2335, 2009. View at Publisher · View at Google Scholar · View at PubMed
  82. E. Pollex, A. Lubetsky, and G. Koren, “The role of placental breast cancer resistance protein in the efflux of glyburide across the human placenta,” Placenta, vol. 29, no. 8, pp. 743–747, 2008. View at Publisher · View at Google Scholar · View at PubMed
  83. A. Floreani, I. Carderi, D. Paternoster et al., “Hepatobiliary phospholipid transporter ABCB4, MDR3 gene variants in a large cohort of Italian women with intrahepatic cholestasis of pregnancy,” Digestive and Liver Disease, vol. 40, no. 5, pp. 366–370, 2008. View at Publisher · View at Google Scholar · View at PubMed
  84. L. Zhou, S. B. Naraharisetti, H. Wang, J. D. Unadkat, M. F. Hebert, and Q. Mao, “The breast cancer resistance protein (Bcrp1/Abcg2) limits fetal distribution of glyburide in the pregnant mouse: an Obstetric-Fetal Pharmacology Research Unit Network and University of Washington Specialized Center of Research Study,” Molecular Pharmacology, vol. 73, no. 3, pp. 949–959, 2008. View at Publisher · View at Google Scholar · View at PubMed
  85. J. S. Wang, D. J. Newport, Z. N. Stowe, J. L. Donovan, P. B. Pennell, and C. L. DeVane, “The emerging importance of transporter proteins in the psychopharmacological treatment of the pregnant patient,” Drug Metabolism Reviews, vol. 39, no. 4, pp. 723–746, 2007. View at Publisher · View at Google Scholar · View at PubMed
  86. F. Azzaroli, A. Mennone, V. Feletti et al., “Clinical trial: modulation of human placental multidrug resistance proteins in cholestasis of pregnancy by ursodeoxycholic acid,” Alimentary Pharmacology and Therapeutics, vol. 26, no. 8, pp. 1139–1146, 2007. View at Publisher · View at Google Scholar · View at PubMed
  87. V. Keitel, C. Vogt, D. Häussinger, and R. Kubitz, “Combined mutations of canalicular transporter proteins cause severe intrahepatic cholestasis of pregnancy,” Gastroenterology, vol. 131, no. 2, pp. 624–629, 2006. View at Publisher · View at Google Scholar · View at PubMed
  88. K. Ushijima, A. Kimura, T. Inokuchi et al., “Placental transport of bile acids: analysis of bile acids in maternal serum and urine, umbilical cord blood, and amniotic fluid,” Kurume Medical Journal, vol. 48, no. 2, pp. 87–91, 2001.
  89. A. C. Enders and T. N. Blankenship, “Comparative placental structure,” Advanced Drug Delivery Reviews, vol. 38, no. 1, pp. 3–15, 1999. View at Publisher · View at Google Scholar
  90. M. Nagashige, F. Ushigome, N. Koyabu et al., “Basal membrane localization of MRP1 in human placental trophoblast,” Placenta, vol. 24, no. 10, pp. 951–958, 2003. View at Publisher · View at Google Scholar
  91. P. Mylona, J. A. Hoyland, and C. P. Sibley, “Sites of mRNA expression of the cystic fibrosis (CF) and multidrug resistance (MDR1) genes in the human placenta of early pregnancy: no evidence for complementary expression,” Placenta, vol. 20, no. 5-6, pp. 493–496, 1999. View at Publisher · View at Google Scholar · View at PubMed
  92. H. E. U. Meyer Zu Schwabedissen, M. Grube, B. Heydrich et al., “Expression, localization, and function of MRP5 (ABCC5), a transporter for cyclic nucleotides, in human placenta and cultured human trophoblasts: effects of gestational age and cellular differentiation,” American Journal of Pathology, vol. 166, no. 1, pp. 39–48, 2005.
  93. A. A. Mathias, J. Hitti, and J. D. Unadkat, “P-glycoprotein and breast cancer resistance protein expression in human placentae of various gestational ages,” American Journal of Physiology, Regulatory Integrative and Comparative Physiology, vol. 289, no. 4, pp. R963–R969, 2005. View at Publisher · View at Google Scholar · View at PubMed
  94. S. Gil, R. Saura, F. Forestier, and R. Farinotti, “P-glycoprotein expression of the human placenta during pregnancy,” Placenta, vol. 26, no. 2-3, pp. 268–270, 2005. View at Publisher · View at Google Scholar · View at PubMed
  95. A. Macfarland, D. R. Abramovich, S. W. B. Ewen, and C. K. Pearson, “Stage-specific distribution of P-glycoprotein in first-trimester and full-term human placenta,” Histochemical Journal, vol. 26, no. 5, pp. 417–423, 1994. View at Publisher · View at Google Scholar
  96. C. M. Perry and S. Noble, “Saquinavir soft-gel capsule formulation: a review of its use in patients with HIV infection,” Drugs, vol. 55, no. 3, pp. 461–486, 1998. View at Publisher · View at Google Scholar
  97. G. R. Kaufmann, C. Duncombe, P. Cunningham et al., “Treatment response and durability of a double protease inhibitor therapy with saquinavir and ritonavir in an observational cohort of HIV-1-infected individuals,” AIDS, vol. 12, no. 13, pp. 1625–1630, 1998. View at Publisher · View at Google Scholar
  98. T. Koudriakova, E. Iatsimirskaia, I. Utkin et al., “Metabolism of the human immunodeficiency virus protease inhibitors indinavir and ritonavir by human intestinal microsomes and expressed cytochrome P4503A4/3A5: mechanism-based inactivation of cytochrome P4503A by ritonavir,” Drug Metabolism and Disposition, vol. 26, no. 6, pp. 552–561, 1998.
  99. M. T. Huisman, J. W. Smit, H. R. Wiltshire, R. M. W. Hoetelmans, J. H. Beijnen, and A. H. Schinkel, “P-glycoprotein limits oral availability, brain, and fetal penetration of saquinavir even with high doses of ritonavir,” Molecular Pharmacology, vol. 59, no. 4, pp. 806–813, 2001.
  100. J. Alsenz, H. Steffen, and R. Alex, “Active apical secretory efflux of the HIV protease inhibitors saquinavir and ritonavir in Caco-2 cell monolayers,” Pharmaceutical Research, vol. 15, no. 3, pp. 423–428, 1998. View at Publisher · View at Google Scholar
  101. V. A. Eagling, L. Profit, and D. J. Back, “Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the HIV-I protease inhibitor saquinavir by grapefruit juice components,” British Journal of Clinical Pharmacology, vol. 48, no. 4, pp. 543–552, 1999. View at Publisher · View at Google Scholar
  102. M. Mirochnick, B. M. Best, A. M. Stek et al., “Lopinavir exposure with an increased dose during pregnancy,” Journal of Acquired Immune Deficiency Syndromes, vol. 49, no. 5, pp. 485–491, 2008. View at Publisher · View at Google Scholar · View at PubMed
  103. S. Ito, L. Magee, and J. Smallhorn, “Drug therapy for fetal arrhythmias,” Clinics in Perinatology, vol. 21, no. 3, pp. 543–572, 1994.
  104. A. Azancot-Benisty, E. Jacqz-Aigrain, N. M. Guirgis, A. Decrepy, J. F. Oury, and P. Blot, “Clinical and pharmacologic study of fetal supraventricular tachyarrhythmias,” Journal of Pediatrics, vol. 121, no. 4, pp. 608–613, 1992. View at Publisher · View at Google Scholar
  105. E. Teodori, S. Dei, C. Martelli, S. Scapecchi, and F. Gualtieri, “The functions and structure of ABC transporters: implications for the design of new inhibitors of Pgp and MRP1 to control multidrug resistance (MDR),” Current Drug Targets, vol. 7, no. 7, pp. 893–909, 2006. View at Publisher · View at Google Scholar
  106. S. Ito, “Transplacental treatment of fetal tachycardia: implications of drug transporting proteins in placenta,” Seminars in Perinatology, vol. 25, no. 3, pp. 196–201, 2001.
  107. L. S. Hodge and T. S. Tracy, “Alterations in drug disposition during pregnancy: implications for drug therapy,” Expert Opinion on Drug Metabolism and Toxicology, vol. 3, no. 4, pp. 557–571, 2007. View at Publisher · View at Google Scholar · View at PubMed
  108. D. Hirt, J. M. Treluyer, V. Jullien et al., “Pregnancy-related effects on nelfinavir-M8 pharmacokinetics: a population study with 133 women,” Antimicrobial Agents and Chemotherapy, vol. 50, no. 6, pp. 2079–2086, 2006. View at Publisher · View at Google Scholar · View at PubMed
  109. P. Villani, M. Floridia, M. F. Pirillo et al., “Pharmacokinetics of nelfinavir in HIV-1-infected pregnant and nonpregnant women,” British Journal of Clinical Pharmacology, vol. 62, no. 3, pp. 309–315, 2006. View at Publisher · View at Google Scholar · View at PubMed
  110. W. J. Tamminga, J. Wemer, B. Oosterhuis et al., “CYP2D6 and CYP2C19 activity in a large population of Dutch healthy volunteers: indications for oral contraceptive-related gender differences,” European Journal of Clinical Pharmacology, vol. 55, no. 3, pp. 177–184, 1999. View at Publisher · View at Google Scholar
  111. A. J. Claessens, L. J. Risler, S. Eyal, D. D. Shen, T. R. Easterling, and M. F. Hebert, “CYP2D6 mediates 4-hydroxylation of clonidine in vitro: implication for pregnancy-induced changes in clonidine clearance,” Drug Metabolism and Disposition, vol. 38, no. 9, pp. 1393–1396, 2010. View at Publisher · View at Google Scholar · View at PubMed
  112. K. Tsutsumi, T. Kotegawa, S. Matsuki et al., “The effect of pregnancy on cytochrome P4501A2, xanthine oxidase, and N-acetyltransferase activities in humans,” Clinical Pharmacology and Therapeutics, vol. 70, no. 2, pp. 121–125, 2001. View at Publisher · View at Google Scholar · View at PubMed
  113. A. Aldridge, J. Bailey, and A. H. Neims, “The disposition of caffeine during and after pregnancy,” Seminars in Perinatology, vol. 5, no. 4, pp. 310–314, 1981.
  114. J. L. Brazier, J. Ritter, and M. Berland, “Pharmacokinetics of caffeine during and after pregnancy,” Developmental Pharmacology and Therapeutics, vol. 6, no. 5, pp. 315–322, 1983.
  115. C. L. Harden, J. Hopp, T. Y. Ting et al., “Management issues for women with epilepsy—Focus on pregnancy (an evidence-based review): I. Obstetrical complications and change in seizure frequency: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the American Epilepsy Society,” Epilepsia, vol. 50, no. 5, pp. 1229–1236, 2009. View at Publisher · View at Google Scholar · View at PubMed
  116. C. L. Harden, K. J. Meador, P. B. Pennell et al., “Management issues for women with epilepsy—focus on pregnancy (an evidence-based review): II. Teratogenesis and perinatal outcomes: report of the Quality Standards Subcommittee and Therapeutics and Technology Subcommittee of the American Academy of Neurology and the American Epilepsy Society,” Epilepsia, vol. 50, no. 5, pp. 1237–1246, 2009. View at Publisher · View at Google Scholar
  117. C. L. Harden, et al., “Management issues for women with epilepsy—focus on pregnancy (an evidence-based review): III. Vitamin K, folic acid, blood levels, and breast-feeding: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the American Epilepsy Society,” Epilepsia, vol. 50, no. 5, pp. 1247–1255, 2009.
  118. P. B. Pennell, D. J. Newport, Z. N. Stowe, S. L. Helmers, J. Q. Montgomery, and T. R. Henry, “The impact of pregnancy and childbirth on the metabolism of lamotrigine,” Neurology, vol. 62, no. 2, pp. 292–295, 2004.
  119. L. M. Grosso and M. B. Bracken, “Caffeine metabolism, genetics, and perinatal outcomes: a review of exposure assessment considerations during pregnancy,” Annals of Epidemiology, vol. 15, no. 6, pp. 460–466, 2005. View at Publisher · View at Google Scholar · View at PubMed
  120. A. Reimers, G. Helde, and E. Brodtkorb, “Ethinyl estradiol, not progestogens, reduces lamotrigine serum concentrations,” Epilepsia, vol. 46, no. 9, pp. 1414–1417, 2005. View at Publisher · View at Google Scholar · View at PubMed
  121. T. S. Tracy, R. Venkataramanan, D. D. Glover, and S. N. Caritis, “Temporal changes in drug metabolism (CYP1A2, CYP2D6 and CYP3A Activity) during pregnancy,” American Journal of Obstetrics and Gynecology, vol. 192, no. 2, pp. 633–639, 2005. View at Publisher · View at Google Scholar · View at PubMed
  122. W. J. Tamminga, J. Wemer, B. Oosterhuis et al., “CYP2D6 and CYP2C19 activity in a large population of Dutch healthy volunteers: indications for oral contraceptive-related gender differences,” European Journal of Clinical Pharmacology, vol. 55, no. 3, pp. 177–184, 1999. View at Publisher · View at Google Scholar
  123. M. Bologa, B. Tang, J. Klein, A. Tesoro, and G. Koren, “Pregnancy-induced changes in drug metabolism in epileptic women,” Journal of Pharmacology and Experimental Therapeutics, vol. 257, no. 2, pp. 735–740, 1991.
  124. B. L. Carter, C. E. Driscoll, and G. D. Smith, “Theophylline clearance during pregnancy,” Obstetrics and Gynecology, vol. 68, no. 4, pp. 555–559, 1986.
  125. M. S. Yerby, “The use of anticonvulsants during pregnancy,” Seminars in Perinatology, vol. 25, no. 3, pp. 153–158, 2001.
  126. J. O. Miners, R. A. Robson, and D. J. Birkett, “Paracetamol metabolism in pregnancy,” British Journal of Clinical Pharmacology, vol. 22, no. 3, pp. 359–362, 1986.
  127. G. Tomson, N. O. Lunell, A. Sundwall, and A. Rane, “Placental passage of oxazepam and its metabolism in mother and newborn,” Clinical Pharmacology and Therapeutics, vol. 25, no. 1, pp. 74–81, 1979.
  128. D. R. Abernethy, M. Divoll, H. R. Ochs, et al., “Increased metabolic clearance of acetaminophen with oral contraceptive use,” Obstetrics and Gynecology, vol. 60, no. 3, pp. 338–341, 1982.
  129. S. Chen, D. Beaton, N. Nguyen et al., “Tissue-specific, inducible, and hormonal control of the human UDP-glucuronosyltransferase-1 (UGT1) locus,” The Journal of Biological Chemistry, vol. 280, no. 45, pp. 37547–37557, 2005. View at Publisher · View at Google Scholar · View at PubMed
  130. T. Shelepova, A. N. Nafziger, J. Victory et al., “Effect of a triphasic oral contraceptive on drug-metabolizing enzyme activity as measured by the validated cooperstown 5+1 cocktail,” Journal of Clinical Pharmacology, vol. 45, no. 12, pp. 1413–1421, 2005. View at Publisher · View at Google Scholar · View at PubMed
  131. R. T. Webb, L. Howard, and K. M. Abel, “Antipsychotic drugs for non-affective psychosis during pregnancy and postpartum,” Cochrane Database of Systematic Reviews, no. 2, Article ID CD004411, 2004.
  132. L. B. McCullough, J. H. Coverdale, and F. A. Chervenak, “A comprehensive ethical framework for responsibly designing and conducting pharmacologic research that involves pregnant women,” American Journal of Obstetrics and Gynecology, vol. 193, no. 3, pp. 901–907, 2005. View at Publisher · View at Google Scholar · View at PubMed
  133. F. A. Chervenak and L. B. McCullough, “Ethics in obstetrics and gynecology: an overview,” European Journal of Obstetrics Gynecology and Reproductive Biology, vol. 75, no. 1, pp. 91–94, 1997. View at Publisher · View at Google Scholar
  134. F. A. Chervenak and L. B. McCullough, “A comprehensive ethical framework for fetal research and its application to fetal surgery for spina bifida,” American Journal of Obstetrics and Gynecology, vol. 187, no. 1, pp. 10–14, 2002. View at Publisher · View at Google Scholar
  135. K. A. Yonkers, “The treatment of women suffering from depression who are either pregnant or breastfeeding,” American Journal of Psychiatry, vol. 164, no. 10, pp. 1457–1459, 2007. View at Publisher · View at Google Scholar · View at PubMed
  136. B. A. Brody, The Ethics of Biomedical Research: An International Perspective, Oxford University Press, New York, NY, USA, 1st edition, 1998.