Ocular pharmacokinetics of lens epithelial cell-specific immunotoxin 4197X-RA.
The ocular clearance, stability and systemic distribution of a lens epithelial cell-specific immunotoxin were evaluated in adult Dutch Belted rabbits. Immunotoxin 4197X-RA was prepared from a murine monoclonal antibody conjugated by a disulfide linkage to ricin A. After intracameral (i.c.) injection, clearance of the immunotoxin from the eye followed a first-order process. The half-life (t1/2) of immunotoxin in the aqueous humor was 51 min. Accumulation of the immunotoxin in ocular tissues appeared to be associated with aqueous outflow tracts, as it was primarily confined to the iris and the limbal regions of the cornea. No acute metabolism of immunotoxin was observed in the anterior chamber. The immunotoxin was detected in the blood 20 min post-injection and achieved a steady-state level after 40 to 180 min. A slow decline in labeled protein was then observed from 180 min to 24 hr. Systemic clearance of the immunotoxin appeared to occur primarily by way of the kidneys. The present data indicate that immunotoxin 4197X-RA, like other large proteins, is passively cleared from the anterior chamber by aqueous flow, and that little or no acute breakdown occurs in the anterior chamber. It is anticipated that these data, along with results from cytotoxicity studies, will result in the determination of optimal doses and frequency of administration for the use of immunotoxin in human clinical trials.
Crosson
C E
CE
Houston Biotechnology Incorporated, The Woodlands, TX 77381.
Kelleher
P J
PJ
Lam
D M
DM
D000818:Animals; D000867:Anterior Chamber / Q000378:metabolism; D001082:Aqueous Humor / Q000378:metabolism; D005123:Eye / Q000378:metabolism*; D005260:Female; D006207:Half-Life; D000922:Immunotoxins / Q000378:metabolism*; D011817:Rabbits; D012276:Ricin; D013997:Time Factors; D014018:Tissue Distribution
D000922:Immunotoxins; D012276:Ricin