Skip Navigation

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by MATSUZAWA, K.
Right arrow Articles by MAKITA, T.
Right arrow Search for Related Content
PubMed
Right arrow Articles by MATSUZAWA, K.
Right arrow Articles by MAKITA, T.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 1992 Oxford University Press

research-article

The Preclinical Safety Evaluation of Human Monoclonal Antibody against Cytomegalovirus1

KEIKO MATSUZAWA, TAMOTSU KOYAMA, SHIGEKI SUGAWARA, SUNAO IKEGAWA, SATOSHI ASANO, SATOSHI SASAKI, TAKAMI TOMIYAMA, YOSHINORI KASAHARA, YOSHIAKI OKAMIYA, KYOKO INOUE, TOMOHIRO OHTA and TOKUTARO MAKITA

Teijin Institute for Bio-Medical Research Asahigaoka 4-3-2, Hino, Tokyo 191, Japan

Received July 25, 1991; accepted December 20, 1991

The human monoclonal antibody against cytomegalovinis (Mab C23) was examined pharmacokinetically and toxicologically as part of the preclinical studies prior to approval for human use. Rats given repeated intravenous administrations of Mab C23 produced no antibodies against Mab C23 and maintained a blood Mab C23 level in a dose-dependent manner. However, pregnant rabbits produced antibodies against Mab C23. The half-life of Mab C23 in plasma was 15.9 days in rats, which was similar to that of normal human serum {gamma}-globulin (NHSG). Neither behavioral effects nor circulatory disturbance was found in mice, rats, and dogs even after a single intravenous injection of 100 or 200 mg/kg, which corresponds to 50 or 100 times the intended clinical dosage. The repeated doses of 2, 10, or 20 mg/kg of Mab C23 on six occasions with 1- or 2-week intervals elicited a transient decrease in leukocyte counts in rats given 10 or 20 mg/kg, but no adverse effects in cynomolgus monkeys. Mab C23 did not cause any reproductive or developmental toxicity when administered to rats and rabbits at dose levels of 20 mg/kg or less. However, pregnant animals showed lower plasma levels of Mab C23 than non-pregnant animals. The chromosomal aberration test disclosed no clastogenicity in human lymphocytes. An immunostaining for Mab C23 revealed no localizations in several tissues of cynomolgus monkeys given intravenous doses of Mab C23. The preclinical safety evaluation in animals other than rabbits, which produced no antibodies against Mab C23, showed that the behavior of Mab C23 is pharmacokinetically similar to that of NHSG and is as safe as NHSG, which has long been used as a biological agent. However, because there was a difference in blood levels of Mab C23 between pregnant and nonpregnant animals, its clinical administration to pregnant patients should differ from that to non-pregnant patients.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.