Abstract：OBJECTIVE To determine the ex vivo human placental transfer of glyburide from maternal circulation to the fetal circulation in Chinese Hans population. METHODS Perfusion studies were performed on thirty-six placentas from healthy term pregnancies. The circulation of mother-placenta-fetus was set up ex vivo within minutes and accessed by studying spectrometry. Integrity and viability of the placenta were determined by measuring fetal volume loss, pH, pO2, ΔhCG, glucose consumption and lactate production during the perfusion experiments. RESULTS Following 3 h of perfusion, the fetal transfer rate of glyburide was (1.64±0.85)%. The clearance index of glyburide was (0.05±0.03). CONCLUSION These data suggest that tiny amount of glyburide can cross the human placenta. Glyburide could be used as a clinically effective alternative to insulin therapy.
黄桦, 王秋燕, 姚勤, 李骞, 王晶晶, 张峻. 基于人胎盘体外循环灌注模型的格列本脲胎盘透过性研究[J]. 中国药学杂志, 2020, 55(18): 1535-1539.
HUANG Hua, WANG Qiu-yan, YAO Qin, LI Qian, WANG Jing-jing, ZHANG Jun. Transplacental Transfer of Glyburide in the ex vivo Human Placenta Perfusion Model. Chinese Pharmaceutical Journal, 2020, 55(18): 1535-1539.
HOK M,KAPUR A,SACKS D A, et al. The international federation of gynecology and obstetrics (FIGO) initiative on gestational diabetes mellitus: a pragmatic guide for diagnosis, management, and care[J]. Int J Gynaecol Obstet,2015,131(suppl): S173-S211.
[2]
NICHOLSON W, BAPTISTE-ROBERTS K.Oral hypoglycaemic agents during pregnancy: the evidence for effectiveness and safety[J]. Best Pract Res Cl Ob, 2011,25(1):51-36.
[3]
The American College of Obstetricians and Gynecologists. Practice bulletin—gestational diabetes mellitus[J]. Obstet Gynecol,2018,131(2):e49-e64.
[4]
Obstetric Group of the College of Obstetricians and Gynecologists of Chinese Medical Association, Association of Diabetes and Pregnancy Study Group of the College of Perinatal Medicine of Chinese Medical Association.Diagnosis and treatment guideline of pregnancy and diabetes[J]. Chin J Obstet Gynecol, 2014,49(8):561-569.
[5]
JAIN S, ZHARIKOVA O L, RAVINDRAN S, et al. Glyburide metabolism by placentas of healthy and gestational diabetics[J]. Am J Perinatol,2008,25(3):169-174.
[6]
LANGER O,CONWAY D L,BERKUS M D, et al. A comparison of glyburide and insulin in women with gestational diabetes mellitus[J]. N Engl J Med, 2000,343(16):1134-1138.
[7]
MAYMONE A C,BAILLARGEON J P,MENARD J, et al. Oral hypoglycemic agents for gestational diabetes mellitus[J]. Expert Opin Drug Saf,2011,10(2):227-238.
[8]
HUSTON J R,GARCIA-BOURNISSEN F,DAVIS A, et al. The human placental perfusion model:a systematic review and development of a model to predict in vivo transfer of therapeutic drugs[J]. Clin Pharmacol Ther,2011,90(1):67-76.
[9]
HUANG H, ZHANG J, MA R M, et al. Establishment of the human placental perfusion model[J]. Chin J Pharmacol Toxicol(中国药理学与毒理学杂志),2013,27(6):1014-1019.
[10]
HUANG H,WANG J J,LI Q, et al. Transplacental transfer of oseltamivir phosphate and its metabolite oseltamivir carboxylate using the ex vivo human placenta perfusion model in Chinese Hans population[J]. J Matern Fetal Neonatal Med, 2017,30(11):1288-1292.
[11]
ZHENG Q L, ZHOU Q, LI J, et al. Placental transfer of bromocriptine in an ex vivo human placental perfusion model[J]. J Matern Fetal Neonatal Med, 2019,32(7):1155-1159
[12]
HNAT M,BAWDON R E.Transfer of meropenem in the ex vivo human placenta perfusion model[J]. Infect Dis Obstet Gynecol,2005,13(4):223-227.
[13]
HUANG H,ZHANG J,WANG J J, et al. A kind of placenta perfusion system:China, 201720136667.3 [P]. 2017-08-29.
[14]
ZHANG J,HUANG H,YAN C, et al. UFLC-MS/MS determination of glibenclamide in placental perfusate[J]. Chin J Pharm Anal(药物分析杂志),2014,34(1):24-29.
[15]
HUANG H,YAO Q,YAN C, et al. UFLC-MS/MS determination of antipyrine in placental perfusate[J]. Chin Pharm J(中国药学杂志),2013,48(15):1319-1322.
[16]
ELLIOTT B D,SCHENKER S,LANGER O, et al. Comparative placental transport of oral hypoglycemic agents in humans: a model of human placental drug transfer[J]. Am J Obstet Gynecol, 1994, 171(3):653-660.
[17]
ELLIOTT B D,LANGER O,SCHENKER S, et al. Insignificant transfer of glyburide occurs across the human placenta[J]. Am J Obstet Gynecol,1991,165 (4 Pt 1):807-812.
[18]
KRAEMER J,KLEIN J,LUBETSDY A, et al. Perfusion studies of glyburide transfer across the human placenta: implications for fetal safety[J]. Am J Obstet Gynecol,2006,195(1):270-274.
[19]
JONSSON A, RYDBERG T, EKBERG G, et al. Slow elimination of glyburide in NIDDM subjects[J]. Diabetes Care,1994,17(2):142-145.
[20]
KOREN G.Glyburide and fetal safety; transplacental pharmacokinetic considerations[J]. Reprod Toxicol,2001,15(3):227-229.
[21]
NI Z L,MAO Q C.ATP-binding cassette efflux transporters in human placenta[J]. Curr Pharm Biotechnol,2011,12(4):674-685.
[22]
GEDEON C,BEHRAVAN J,KOREN G, et al. Transport of glyburide by placental ABC transporters: implications in fetal drug exposure[J]. Placenta,2006,27(11-12):1096-1102.
2020, Vol. 55 
