European Journal of Obstetrics & Gynecology and Reproductive Biology
Volume 136, Issue 1 , Pages 29-33 , January 2008

Determination of metformin transfer across the human placenta using a dually perfused ex vivo placental cotyledon model

  • Michal Kovo

      Affiliations

    • Department of Obstetrics and Gynecology, the E. Wolfson Medical Center, Holon, and Sackler School of Medicine, Tel Aviv University, Israel
    • These authors contributed equally to this work.
  • ,
  • Simon Haroutiunian

      Affiliations

    • Department of Pharmaceutics, School of Pharmacy, Hebrew University of Jerusalem, Jerusalem, Israel
    • These authors contributed equally to this work.
  • ,
  • Noa Feldman

      Affiliations

    • Department of Obstetrics and Gynecology, the E. Wolfson Medical Center, Holon, and Sackler School of Medicine, Tel Aviv University, Israel
  • ,
  • Amnon Hoffman

      Affiliations

    • Department of Pharmaceutics, School of Pharmacy, Hebrew University of Jerusalem, Jerusalem, Israel
    • Corresponding Author InformationCorresponding author at: Department of Pharmaceutics, School of Pharmacy, Hebrew University of Jerusalem, P.O. Box 12065, 91120 Jerusalem, Israel. Tel.: +972 2675 7014; fax: +972 2675 7246.
  • ,
  • Marek Glezerman

      Affiliations

    • Department of Obstetrics and Gynecology, the E. Wolfson Medical Center, Holon, and Sackler School of Medicine, Tel Aviv University, Israel

Received 13 May 2006 ,Revised 1 January 2007 ,Accepted 9 January 2007.

References 

  1. Coetzee EJ, Jackson WP. Metformin in management of pregnant insulin-independent diabetics. Diabetologia. 1979;16:241–245
  2. Piacquadio K, Hollingsworth DR, Murphy H. Effects of in-utero exposure to oral hypoglycaemic drugs. Lancet. 1991;338:866–869
  3. Hellmuth E, Damm P, Molsted-Pedersen L. Oral hypoglycaemic agents in 118 diabetic pregnancies. Diabet Med. 2000;17:507–511
  4. Gutzin SJ, Kozer E, Magee LA, Feig DS, Koren G. The safety of oral hypoglycemic agents in the first trimester of pregnancy: a meta-analysis. Can J Clin Pharmacol. 2003;10:179–183
  5. Moor L, Briery C, Martin R, Hood E, Bofill J, Morrison J. Metformin vs. insulin in A2 diabetics; a randomized clinical trial. Am J Obstet Gynecol. 2005;191:17
  6. Glueck CJ, Wang P, Fontaine R, Tracy T, Sieve-Smith L. Metformin-induced resumption of normal menses in 39 of 43 (91%) previously amenorrheic women with the polycystic ovary syndrome. Metabolism. 1999;48:511–519
  7. Glueck CJ, Goldenberg N, Wang P, Loftspring M, Sherman A. Metformin during pregnancy reduces insulin, insulin resistance, insulin secretion, weight, testosterone and development of gestational diabetes: prospective longitudinal assessment of women with polycystic ovary syndrome from preconception throughout pregnancy. Hum Reprod. 2004;19:510–521
  8. Lord JM, Flight IH, Norman RJ. Insulin-sensitising drugs (metformin, troglitazone, rosiglitazone, pioglitazone, d-chiro-inositol) for polycystic ovary syndrome. Cochrane Database Syst Rev. 2003;CD003053
  9. Glueck CJ, Phillips H, Cameron D, Sieve-Smith L, Wang P. Continuing metformin throughout pregnancy in women with polycystic ovary syndrome appears to safely reduce first-trimester spontaneous abortion: a pilot study. Fertil Steril. 2001;75:46–52
  10. Jakubowicz DJ, Iuorno MJ, Jakubowicz S, Roberts KA, Nestler JE. Effects of metformin on early pregnancy loss in the polycystic ovary syndrome. J Clin Endocrinol Metab. 2002;87:524–529
  11. Glueck CJ, Bornovali S, Pranikoff J, Goldenberg N, Dharashivkar S, Wang P. Metformin, pre-eclampsia, and pregnancy outcomes in women with polycystic ovary syndrome. Diabet Med. 2004;21:829–836
  12. Glueck CJ, Goldenberg N, Streicher P, Wang P. Metformin and gestational diabetes. Curr Diab Rep. 2003;3:303–312
  13. Elliott BD, Langer O, Schenker S, Johnson RF. Insignificant transfer of glyburide occurs across the human placenta. Am J Obstet Gynecol. 1991;165:807–812
  14. Elliott BD, Schenker S, Langer O, Johnson R, Prihoda T. Comparative placental transport of oral hypoglycemic agents in humans: a model of human placental drug transfer. Am J Obstet Gynecol. 1994;171:653–660
  15. Langer O, Conway DL, Berkus MD, Xenakis EM, Gonzales O. A comparison of glyburide and insulin in women with gestational diabetes mellitus. N Engl J Med. 2000;343:1134–1138
  16. Jacobson GF, Ramos GA, Ching JY, Kirby RS, Ferrara A, Field DR. Comparison of glyburide and insulin for the management of gestational diabetes in a large managed care organization. Am J Obstet Gynecol. 2005;193:118–124
  17. McCarthy EA, Walker SP, McLachlan K, Boyle J, Permezel M. Metformin in obstetric and gynecologic practice: a review. Obstet Gynecol Surv. 2004;59:118–127
  18. Norman RJ, Wang JX, Hague W. Should we continue or stop insulin sensitizing drugs during pregnancy?. Curr Opin Obstet Gynecol. 2004;16:245–250
  19. Wang DS, Kusuhara H, Kato Y, Jonker JW, Schinkel AH, Sugiyama Y. Involvement of organic cation transporter 1 in the lactic acidosis caused by metformin. Mol Pharmacol. 2003;63:844–848
  20. Kimura N, Masuda S, Tanihara Y, et al. Metformin is a superior substrate for renal organic cation transporter OCT2 rather than hepatic OCT1. Drug Metab Pharmacokinet. 2005;20:379–386
  21. Kimura N, Okuda M, Inui K. Metformin transport by renal basolateral organic cation transporter hOCT2. Pharm Res. 2005;22:255–259
  22. Schneider H, Huch A. Dual in vitro perfusion of an isolated lobe of human placenta: method and instrumentation. Contrib Gynecol Obstet. 1985;13:40–47
  23. AbuRuz S, Millership J, McElnay J. Determination of metformin in plasma using a new ion pair solid phase extraction technique and ion pair liquid chromatography. J Chromatogr B Analyt Technol Biomed Life Sci. 2003;798:203–209
  24. Schneider H, Panigel M, Dancis J. Transfer across the perfused human placenta of antipyrine, sodium and leucine. Am J Obstet Gynecol. 1972;114:822–828
  25. Bourget P, Roulot C, Fernandez H. Models for placental transfer studies of drugs. Clin Pharmacokinet. 1995;28:161–180
  26. Lagrange FJ, Brun JL, Clot PF, et al. Placental transfer of SR49059 in the human dually perfused cotyledon in vitro. Placenta. 2001;22:870–875
  27. Unadkat JD, Dahlin A, Vijay S. Placental drug transporters. Curr Drug Metab. 2004;5:125–131
  28. Vanky E, Zahlsen K, Spigset O, Carlsen SM. Placental passage of metformin in women with polycystic ovary syndrome. Fertil Steril. 2005;83:1575–1578

PII: S0301-2115(07)00080-2

doi: 10.1016/j.ejogrb.2007.01.013

European Journal of Obstetrics & Gynecology and Reproductive Biology
Volume 136, Issue 1 , Pages 29-33 , January 2008