title: Potential seminal transport of pharmaceuticals to the conceptus.
abstract: Small molecule pharmaceutical products are assumed to reach concentrations in semen similar to those in blood plasma. Exposure modeling for these small-molecule products in humans assumes a daily dose of 5mL of semen and 100% absorption from the vagina with distribution to the conceptus through the maternal systemic circulation. Monoclonal antibody drugs are present in semen at concentrations about 2% or less of those in blood, and the modeling used for small molecules will over-estimate the possibility of conceptus exposure to immunoglobulins. It is not known whether peptide products reach semen, but in general peptide medications are destroyed by vaginal peptidases, and conceptus exposure is predicted to be minimal. Theoretical exposure routes to pharmaceuticals that might result in exposure of the conceptus greater than that of maternal systemic exposures include direct access through the cervical canal, adsorption to sperm for carriage into the oocyte, and direct delivery from the vaginal veins or lymphatics to the uterine artery. There is some evidence for direct access to the uterus for progesterone, terbutaline, and danazol, but the evidence does not involve exposures during pregnancy in most instances. Studies in mice, rats, rabbits, and monkeys do not suggest that exposure to small molecule pharmaceuticals in semen imposes risks to the conceptus beyond those that can be predicted using modeling of systemic maternal exposure. Monoclonal antibody and peptide exposure in semen does not pose a significant risk to the conceptus.
authors.affiliation: Reproductive Toxicology Center and Scialli Consulting LLC, Washington DC, USA. Electronic address: ascialli@scialliconsulting.com.
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Scialli
authors.affiliation: Janssen R&D, Beerse, Belgium.
authors.forename: Graham
authors.initials: G
authors.lastname: Bailey
authors.affiliation: Sanofi U. S. Inc., Bridgewater, NJ, USA.
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Beyer
authors.affiliation: Novo Nordisk A/S, Måløv, Denmark.
authors.forename: Ingrid Brück
authors.initials: IB
authors.lastname: Bøgh
authors.affiliation: Lilly Research Laboratories, Indianapolis, IN, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Breslin
authors.affiliation: ILSI-Health and Environmental Sciences Institute, Washington DC, USA.
authors.forename: Connie L
authors.initials: CL
authors.lastname: Chen
authors.affiliation: Novartis Pharmaceutical Corporation, East Hanover, NJ, USA.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: DeLise
authors.affiliation: Celgene Corporation, Summit, NJ, USA.
authors.forename: Julia Y
authors.initials: JY
authors.lastname: Hui
authors.affiliation: Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Moffat
authors.affiliation: ApconiX Ltd., Macclesfield, UK.
authors.forename: Jane
authors.initials: J
authors.lastname: Stewart
authors.affiliation: Bristol-Meyers Squibb, New Brunswick, NJ, USA.
authors.forename: Kary E
authors.initials: KE
authors.lastname: Thompson
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000378:metabolism*; D001692:Biological Transport; D002584:Cervix Uteri / Q000187:drug effects / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011247:Pregnancy; D011506:Proteins / Q000009:adverse effects / Q000378:metabolism*; D018570:Risk Assessment; D012307:Risk Factors; D012661:Semen / Q000378:metabolism*; D013045:Species Specificity; D014621:Vagina / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D004364:Pharmaceutical Preparations; D011506:Proteins
keywords: Male-mediated pregnancy effects; Monoclonal antibodies; Peptides; Pharmaceuticals; Semen