title: Pharmacokinetics and ovarian-stimulatory effects of equine and human chorionic gonadotropins administered singly and in combination in the domestic cat.
abstract: Pregnancy success and embryo survival are low with the use of assisted reproduction in felids treated with exogenous gonadotropins. In this study, the pharmacokinetics and ovarian-stimulatory effects of eCG and hCG were evaluated in the domestic cat. Catheterized anestrual queens (n = 4 per treatment [Trt] group) were given 100 IU eCG i.v. (Trt 1), 100 IU eCG i.m. (Trt 2), 75 IU hCG i.v. (Trt 3), 75 IU hCG i.m. (Trt 4), or 100 IU eCG i.m. followed 80 h later by 75 IU hCG i.m. (Trt 5). Blood samples were collected at 0, 5, 30, and 60 min and 4, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 h postinjection, and serum samples were analyzed for estradiol-17beta, progesterone, eCG, and hCG. Pharmacokinetic traits (volume of distribution, Vd; elimination half-life, t1/2beta; clearance rate, Clr) were calculated for eCG and hCG. When i.v. and i.m. administration were compared, no differences (p > 0.05) were observed in follicle or corpus luteum (CL) number or hormone concentrations for queens receiving eCG or hCG alone. Number of mature ovarian follicles (> or = 2 mm diameter) observed at 168 h postinjection did not differ (p > 0.05) for eCG (mean +/- SEM, 10.5 +/- 2.0) vs. hCG (11.1 +/- 3.0), indicating that these were equally effective in inducing follicular growth. In most queens (> 90%) given single gonadotropins (i.m. or i.v.), eCG and hCG persisted in circulation for at least 120 h and 96 h after injection, respectively, reflecting similar (p > 0.05) pharmacokinetic (i.v.) values for Vd (eCG, 91.4 +/- 24.8 ml/kg; hCG, 59.1 +/- 7.9 ml/kg), t1/2beta (eCG, 23.0 +/- 2.4 h; hCG, 22.9 +/- 4.1 h), and Clr (eCG, 2.7 +/- 0.5 ml/h per kg; hCG, 1.8 +/- 0.1 ml/h per kg). Sequential treatment with eCG+hCG did not affect (p > 0.05) the t1/2beta of individual gonadotropins. In summary, eCG and hCG have comparable pharmacokinetics and ovarian-stimulatory activity when administered alone to the domestic cat. These findings suggest that hCG promotes the ancillary follicle formation that is frequently observed after ovulation in cats treated with eCG+hCG regimens, possibly disrupting the maternal environment and decreasing fecundity following assisted reproductive procedures.
authors.affiliation: Conservation & Research Center, National Zoological Park, Smithsonian Institution, Front Royal, Virginia 22630, USA. nzpcrc18@sivm.si.edu
authors.forename: W F
authors.initials: WF
authors.lastname: Swanson
authors.forename: B A
authors.initials: BA
authors.lastname: Wolfe
authors.forename: J L
authors.initials: JL
authors.lastname: Brown
authors.forename: T
authors.initials: T
authors.lastname: Martin-Jimenez
authors.forename: J E
authors.initials: JE
authors.lastname: Riviere
authors.forename: T L
authors.initials: TL
authors.lastname: Roth
authors.forename: D E
authors.initials: DE
authors.lastname: Wildt
mesh_terms: D000818:Animals; D002415:Cats / Q000502:physiology*; D006063:Chorionic Gonadotropin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D004958:Estradiol / Q000097:blood; D005260:Female; D006062:Gonadotropins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D006080:Ovarian Follicle / Q000502:physiology; D010053:Ovary / Q000187:drug effects*; D011247:Pregnancy; D011374:Progesterone / Q000097:blood
chemical_list: D006063:Chorionic Gonadotropin; D006062:Gonadotropins; D011374:Progesterone; D004958:Estradiol