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The Inhibin B Response in Male Rats Treated with Two Drug Candidates.
MedLine Citation:
PMID:  23348891     Owner:  NLM     Status:  Publisher    
BACKGROUND: Serum Inhibin B was measured in two studies of known testis-toxic drug candidates. METHODS AND RESULTS: Study 1 was for a compound for Hepatitis C, and utilized a 10-week dosing period, followed by mating and necropsy of half of each group, and then a 12-week recovery period for the remaining animals. At the postmating necropsy, 6 of 15 high-dose males had testis lesions; Inhibin B was significantly reduced in all animals in that group. The mid-dose group had no lesions but significantly reduced serum Inhibin B. At recovery, 9 of 15 high-dose males showed damage in testes; serum Inhibin B levels were not different from controls. Inhibin B appeared to both overreport and underreport testis damage in Study 1. Study 2 was an acute pathogenesis study for an antibacterial compound, using control and two dose levels and multiple time points (days 5, 8, 15, 22, and then untreated until day 71). At each time point blood was sampled from all remaining rats and five/group were killed for histologic evaluation. The low-dose group had minimal to moderate lesions, while serum Inhibin B was never changed. The high-dose animals progressed quickly from minimal lesions to being broadly and moderately affected; serum Inhibin B levels were reduced at days 8 and 15 only. In Study 2, Inhibin B appeared less sensitive than histology, except at the extremes of testis damage, when Inhibin B was routinely low. CONCLUSION: We conclude that in these two studies there was a poor correlation between changes in serum levels of Inhibin B and testis histopathology.
Robert E Chapin; James D Alvey; Richard A Goldstein; Melba G Dokmanovich; William J Reagan; Kjell Johnson; Frank J Geoly
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-24
Journal Detail:
Title:  Birth defects research. Part B, Developmental and reproductive toxicology     Volume:  -     ISSN:  1542-9741     ISO Abbreviation:  Birth Defects Res. B Dev. Reprod. Toxicol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101155115     Medline TA:  Birth Defects Res B Dev Reprod Toxicol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2013 Wiley Periodicals, Inc.
Developmental and Reproductive Toxicology Group, Drug Safety Research and Development, Pfizer Global R&D, Groton, Connecticut.
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