title: Evaluation of the maternal-fetal transfer of granisetron in an ex vivo placenta perfusion model.
abstract: The objective of this study was to estimate maternal-fetal transplacental passage of granisetron in an ex vivo placental perfusion model. Term human placentas (N=8) were collected immediately after delivery. A single cotyledon from each placenta was perfused granisetron concentration to mimic systemic maternal peak plasma concentrations following either IV (50ng/mL) or transdermal administration (5ng/mL). To assess drug transfer and accumulation, samples were collected from maternal and fetal compartments. In the 50ng/mL open model, the mean transport fraction was 0.21±0.08 with clearance index of 0.53±0.66. Fetal peak concentrations achieved was 5.6±6.6ng/mL with mean accumulation of 5.35±6.4ng/mL. No drug was detected in the fetal compartment with the 5ng/mL models. Transplacental passage of granisetron was inconsistent at the 50ng/mL concentration that achieved with IV dosing. However, there consistently was no detectable passage in all the placentas evaluated of the granisetron at 5ng/mL concentration that would be achieved after transdermal patch administration.
authors.affiliation: Division of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Julius
authors.affiliation: Department of Gynecologic Oncology & Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
authors.forename: Andrew
authors.initials: A
authors.lastname: Tindall
authors.affiliation: Department of Gynecology, Obstetrics & Reproductive Sciences, The University of Texas Health Sciences Center at Houston Medical School, Houston, TX, United States.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Moise
authors.affiliation: Department of Gynecology, Obstetrics & Reproductive Sciences, The University of Texas Health Sciences Center at Houston Medical School, Houston, TX, United States.
authors.forename: Jerrie S
authors.initials: JS
authors.lastname: Refuerzo
authors.affiliation: Department of Gynecology, Obstetrics & Reproductive Sciences, The University of Texas Health Sciences Center at Houston Medical School, Houston, TX, United States.
authors.forename: Pamela D
authors.initials: PD
authors.lastname: Berens
authors.affiliation: Division of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX, United States; Department of Gynecologic Oncology & Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States; Department of Gynecology, Obstetrics & Reproductive Sciences, The University of Texas Health Sciences Center at Houston Medical School, Houston, TX, United States. Electronic address: judith.ann.smith@uth.tmc.edu.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Smith
mesh_terms: D000279:Administration, Cutaneous; D061605:Administration, Intravenous; D000932:Antiemetics / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D017829:Granisetron / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008431:Maternal-Fetal Exchange / Q000187:drug effects*; D008954:Models, Biological; D010920:Placenta / Q000187:drug effects; D011247:Pregnancy
chemical_list: D000932:Antiemetics; D017829:Granisetron
keywords: Granisetron; Nausea; Placental perfusion; Pregnancy; Vomiting