Assessment of fetal exposure risk following seminal excretion of a therapeutic IgG4 (T-IgG4) monoclonal antibody using a rabbit model

Reproductive Toxicology

Volumn 48, Issue , 2014, Pages 124-131

  Breslin, William J ^a   Hilbish, Kim G ^a   Page, Todd J ^a   Coutant, David E ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

IgG; Monoclonal antibodies; Placental transfer; Seminal transfer; Vaginal absorption

Indexed keywords

IMMUNOGLOBULIN G ANTIBODY; MONOCLONAL ANTIBODY; THERAPEUTIC IMMUNOGLOBULIN G4 MONOCLONAL ANTIBODY; UNCLASSIFIED DRUG; IMMUNOGLOBULIN G;

ADULT; ANIMAL EXPERIMENT; ANTIBODY BLOOD LEVEL; ARTICLE; BIOLOGICAL MODEL; CONTROLLED STUDY; DOSE TIME EFFECT RELATION; DRUG ABSORPTION; DRUG DISTRIBUTION; DRUG ELIMINATION; DRUG TRANSPORT; FEMALE; FETUS; GESTATIONAL AGE; IN VIVO STUDY; LIMIT OF QUANTITATION; MALE; MAXIMUM PLASMA CONCENTRATION; MORTALITY; NEW ZEALAND WHITE (RABBIT); NONHUMAN; PLACENTAL TRANSFER; PRENATAL DRUG EXPOSURE; RISK ASSESSMENT; SEMEN ANALYSIS; SEMINAL EXCRETION; SEMINAL TRANSFER; SINGLE DRUG DOSE; TIME TO MAXIMUM PLASMA CONCENTRATION; TOXICITY TESTING; TOXICOKINETICS; VAGINAL ABSORPTION; ANIMAL; BLOOD; FETOMATERNAL TRANSFUSION; INTRAVAGINAL DRUG ADMINISTRATION; INTRAVENOUS DRUG ADMINISTRATION; METABOLISM; PLACENTA; PREGNANCY; RABBIT; SPERM; VAGINA;

ORYCTOLAGUS CUNICULUS;

ADMINISTRATION, INTRAVAGINAL; ANIMALS; ANTIBODIES, MONOCLONAL; FEMALE; FETUS; IMMUNOGLOBULIN G; INJECTIONS, INTRAVENOUS; MALE; MATERNAL-FETAL EXCHANGE; PLACENTA; PREGNANCY; RABBITS; SEMEN; VAGINA;

EID: 84906789855     PISSN: 08906238     EISSN: 18731708     Source Type: Journal    
DOI: 10.1016/j.reprotox.2014.05.004     Document Type: Article

References (16)

1. Pichini S., Zuccaro P., Pacifici R. Drugs in semen. Clin Pharmacokinet 1994, 26(5):356-373.
2. Klemmt L., Scialli R. Review Article. The transport of chemicals in semen. Birth Defects Res B Dev Reprod Toxicol 2005, 77:119-131.
3. Milingos S., Creatsas G., Kallipolitis G., Lolis D., Pavlotos L.D., Kaskarelis D. An appraisal of cephalexin and clinamycin concentration in seminal plasma. Acta Eur Fertil 1981, 12(4):319-321.
4. ICH, International Conference on Harmonization Detection of toxicity to reproduction for medicinal products and toxicity to male fertility S5 (R2) 2005.
5. UK, United Kingdom Clarification of contraceptive wording in clinical trials conducted in the UK 2010, http://lillynetcollaboration.global.lilly.com/sites/GMRS_GPS/SAN/Document_Library/20100521_Guidelines_In_Clinical_Trials_UK_v.2.pdf.
6. Roopenian D.C., Akilesh S. FcRn: the neonatal Fc receptor comes of age. Nat Rev Immunol 2007, 7:715-725.
7. Keizer R.J., Huitema D.R., Schelens J.H.M., Beijnen J.H. Clinical pharmacokinetics of therapeutic monoclonal antibodies. Clin Pharmacokinet 2010, 49(8):493-507.
8. Li Z., Palaniyandi S., Zeng R., Tuo W., Roopenian D.C., Zhu X. Transfer of IgG in the female genital track by MHC class I-related Fc receptor (FcRn) confers protective immunity to vaginal infection. Proc Natl Acad Sci USA 2011, 108(11):4388-4393.
9. Suarez S.S. Interactions of spermatozoa with the female reproductive tract: inspiration for assisted reproduction. Reprod Fertil Dev 2007, 19(1):103-110.
10. Becher N., Waldort K.A., Hein M., Uldbjerg N. The cervical mucus plug: structured review of the literature. Acta Obstet Gynecol Scand 2009, 88:502-513.
11. Knee R.A., Hickey D.K., Beagley K.W., Jones R.C. Transport of IgG across the blood-luminal barrier of the male reproductive tract of the rat and the effect of estradiol administration on reabsorption of fluid and IgG by the epididymal ducts. Biol Reprod 2005, 73(4):688-694.
12. Raux M., Finkielsztejn L., Salmon-Ceron D., Bouchez H., Exclear J.L., Dulioust E., et al. IgG subclass distribution in serum and various mucosal fluids of HIV type 1-infected subjects. AIDS Res Hum Retroviruses 2000, 16(2):583-594.
13. Oyeyinka G.O., Bello C.S.S., Elegba O.Y., Nsofor B.I. Secretory IgA and other proteins in semen from healthy Nigerian men. J Reprod Med 1990, 35(4):375-379.
14. Bowman C.J., Breslin W.J., Connor A.V., Martin P.L., Moffat G.J., Sivaraman L., et al. Placental transfer of Fc-containing biopharmaceuticals, an industry survey analyses. Birth Defects Res B Dev Reprod Toxicol 2013, 98:459-485.
15. Pentsuk N., van der Laan J.W. An interspecies comparison of placental antibody transfer: new insights into developmental toxicity testing of monoclonal antibodies. Birth Defects Res B Dev Reprod Toxicol 2009, 86(4):328-344.
16. Eskenazi B., Wyrobek A.J., Sloter E., Kidd S.A., Moore L., Young S., et al. The association of age and semen quality in healthy men. Human Reprod 2003, 18(2):447-454.