TY - JOUR T1 - Metabolism and Disposition of Bupropion in Pregnant Baboons (<em>Papio cynocephalus</em>) JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 1773 LP - 1779 DO - 10.1124/dmd.114.058255 VL - 42 IS - 10 AU - Erik Rytting AU - Xiaoming Wang AU - Daria I. Vernikovskaya AU - Ying Zhan AU - Cassondra Bauer AU - Susan M. Abdel-Rahman AU - Mahmoud S. Ahmed AU - Tatiana N. Nanovskaya Y1 - 2014/10/01 UR - http://dmd.aspetjournals.org/content/42/10/1773.abstract N2 - 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 Cmax (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. AUCOH-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. ER -