Transplacental transfer and metabolism of buprenorphine in preterm human placenta.
We sought to determine whether gestational age affects the transplacental transfer and metabolism of buprenorphine (BUP). Transfer of BUP (10 ng/mL) and its [ (3)H]-isotope was determined across placentas of 30 to 34 weeks of gestation utilizing the technique of dual perfusion of placental lobule. Concentration of the drug in trophoblast tissue and in maternal and fetal circuits was determined by liquid scintillation spectrometry. Microsomes prepared from placentas of 17 to 37 weeks of gestation were divided into three groups: late second, early third, and late third trimesters. Antibodies raised against human cytochrome P450 (CYP) isoforms were utilized to identify the enzyme(s) catalyzing BUP biotransformation by preterm placental microsomes. The amount of norbuprenorphine formed was determined by liquid chromatography-mass spectrometry (LC-MS). BUP transfer across the placentas of 30 to 34 weeks of gestation was similar to those at term. CYP19 antibodies caused 60% inhibition of BUP metabolism by microsomes of late second and early third trimesters and 85% by microsomes of late third trimester. The developmental changes occurring in human placenta between 30 weeks of gestation through term do not affect the transfer of BUP across human placenta. CYP19 is the major enzyme responsible for biotransformation of BUP beginning at 17 weeks of gestation until term.
Fokina
Valentina M
VM
Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas 77555-0587, USA.
Patrikeeva
Svetlana L
SL
Zharikova
Olga L
OL
Nanovskaya
Tatiana N
TN
Hankins
Gary V D
GV
Ahmed
Mahmoud S
MS
D000911:Antibodies, Monoclonal; D001141:Aromatase / Q000276:immunology / Q000378:metabolism; D001189:Aryl Hydrocarbon Hydroxylases / Q000276:immunology / Q000378:metabolism; D001711:Biotransformation; D002047:Buprenorphine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics*; D065702:Cytochrome P-450 CYP2B6; D065727:Cytochrome P-450 CYP2C8; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D005865:Gestational Age; D006801:Humans; D066298:In Vitro Techniques; D008861:Microsomes / Q000201:enzymology*; D010089:Oxidoreductases, N-Demethylating / Q000276:immunology / Q000378:metabolism; D010477:Perfusion; D010920:Placenta / Q000201:enzymology* / Q000502:physiology; D011247:Pregnancy
D000911:Antibodies, Monoclonal; D002047:Buprenorphine; C043585:norbuprenorphine; D003577:Cytochrome P-450 Enzyme System; D001141:Aromatase; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; C450259:CYP2C8 protein, human; D065702:Cytochrome P-450 CYP2B6; D065727:Cytochrome P-450 CYP2C8; D010089:Oxidoreductases, N-Demethylating