title: Metabolism and disposition of bupropion in pregnant baboons (Papio cynocephalus).
abstract: Recent in vitro data obtained in our laboratory revealed similarities between baboons and humans in the biotransformation of bupropion (BUP) by both hepatic and placental microsomes. These data supported the use of baboons to study BUP biotransformation during pregnancy. The aim of this investigation was to determine the pharmacokinetics of BUP in baboons during pregnancy and postpartum, as well as fetal exposure to the drug after intravenous administration. Pregnant baboons (n = 5) received a single intravenous bolus dose of bupropion hydrochloride (1 mg/kg) at gestational ages 94-108 days (midpregnancy), 142-156 days (late pregnancy), and 6 weeks postpartum. Blood and urine samples were collected for 12 and 24 hours, respectively. The concentrations of BUP, hydroxybupropion (OH-BUP), threohydrobupropion, and erythrohydrobupropion in plasma were determined by liquid chromatography-tandem mass spectrometry. Relative to the postpartum period, the average midpregnancy clearance of BUP trended higher (3.6 ± 0.15 versus 2.7 ± 0.28 l/h per kg) and the average C(max) (294 ± 91 versus 361 ± 64 ng/ml) and the area under the curve (AUC) of BUP values (288 ± 22 versus 382 ± 42 h·ng/ml) trended lower. AUC(OH-BUP) also tended to be lower midpregnancy compared with postpartum (194 ± 76 versus 353 ± 165 h·ng/ml). Whereas the observed trend toward increased clearance of BUP during baboon pregnancy could be associated with a pregnancy-induced increase in its biotransformation, the trend toward increased renal elimination of OH-BUP may overshadow any corresponding change in the hydroxylation activity of CYP2B.
authors.affiliation: Department of Obstetrics & Gynecology, University of Texas Medical Branch at Galveston, Galveston, Texas (E.R., X.W., D.I.V., Y.Z., M.S.A., T.N.N.); Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, Texas (C.B.); and Division of Clinical Pharmacology and Medical Toxicology, Children's Mercy Hospital, Kansas City, Missouri (S.M.A.-R.).
authors.forename: Erik
authors.initials: E
authors.lastname: Rytting
authors.affiliation: Department of Obstetrics & Gynecology, University of Texas Medical Branch at Galveston, Galveston, Texas (E.R., X.W., D.I.V., Y.Z., M.S.A., T.N.N.); Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, Texas (C.B.); and Division of Clinical Pharmacology and Medical Toxicology, Children's Mercy Hospital, Kansas City, Missouri (S.M.A.-R.).
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Obstetrics & Gynecology, University of Texas Medical Branch at Galveston, Galveston, Texas (E.R., X.W., D.I.V., Y.Z., M.S.A., T.N.N.); Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, Texas (C.B.); and Division of Clinical Pharmacology and Medical Toxicology, Children's Mercy Hospital, Kansas City, Missouri (S.M.A.-R.).
authors.forename: Daria I
authors.initials: DI
authors.lastname: Vernikovskaya
authors.affiliation: Department of Obstetrics & Gynecology, University of Texas Medical Branch at Galveston, Galveston, Texas (E.R., X.W., D.I.V., Y.Z., M.S.A., T.N.N.); Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, Texas (C.B.); and Division of Clinical Pharmacology and Medical Toxicology, Children's Mercy Hospital, Kansas City, Missouri (S.M.A.-R.).
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhan
authors.affiliation: Department of Obstetrics & Gynecology, University of Texas Medical Branch at Galveston, Galveston, Texas (E.R., X.W., D.I.V., Y.Z., M.S.A., T.N.N.); Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, Texas (C.B.); and Division of Clinical Pharmacology and Medical Toxicology, Children's Mercy Hospital, Kansas City, Missouri (S.M.A.-R.).
authors.forename: Cassondra
authors.initials: C
authors.lastname: Bauer
authors.affiliation: Department of Obstetrics & Gynecology, University of Texas Medical Branch at Galveston, Galveston, Texas (E.R., X.W., D.I.V., Y.Z., M.S.A., T.N.N.); Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, Texas (C.B.); and Division of Clinical Pharmacology and Medical Toxicology, Children's Mercy Hospital, Kansas City, Missouri (S.M.A.-R.).
authors.forename: Susan M
authors.initials: SM
authors.lastname: Abdel-Rahman
authors.affiliation: Department of Obstetrics & Gynecology, University of Texas Medical Branch at Galveston, Galveston, Texas (E.R., X.W., D.I.V., Y.Z., M.S.A., T.N.N.); Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, Texas (C.B.); and Division of Clinical Pharmacology and Medical Toxicology, Children's Mercy Hospital, Kansas City, Missouri (S.M.A.-R.).
authors.forename: Mahmoud S
authors.initials: MS
authors.lastname: Ahmed
authors.affiliation: Department of Obstetrics & Gynecology, University of Texas Medical Branch at Galveston, Galveston, Texas (E.R., X.W., D.I.V., Y.Z., M.S.A., T.N.N.); Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, Texas (C.B.); and Division of Clinical Pharmacology and Medical Toxicology, Children's Mercy Hospital, Kansas City, Missouri (S.M.A.-R.) tnnanovs@utmb.edu.
authors.forename: Tatiana N
authors.initials: TN
authors.lastname: Nanovskaya
mesh_terms: D000818:Animals; D001711:Biotransformation; D016642:Bupropion / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics* / Q000652:urine; D005260:Female; D048548:Papio cynocephalus / Q000097:blood / Q000378:metabolism* / Q000652:urine; D049590:Postpartum Period / Q000097:blood / Q000378:metabolism / Q000652:urine; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000097:blood / Q000378:metabolism* / Q000652:urine
chemical_list: D016642:Bupropion
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