An enzyme immunoassay for determining plasma concentrations of didemnin B.
Didemnin A was conjugated at the amino terminus of the N-methylleucine residue, via the linkers N-succinimidyl-3-(2-pyridyldithio)-propionate and trans-1,4-maleimidomethyl-cyclohexane carboxylic acid, to keyhole limpet hemocyanin (KLH) and bovine serum albumin (BSA). The didemnin-KLH conjugates were used to hyperimmunize rabbits. The resulting high titer antisera were employed with didemnin-BSA conjugate-coated microtiter plate wells to develop an indirect competitive inhibition enzyme immunoassay (CIEIA) that was fully cross reactive with didemnin B. A CIEIA is described that is capable of detecting the drug in plasma from didemnin B-treated patients at concentrations down to 1-3 ng/ml. This simple, sensitive CIEIA has been employed to demonstrate plasma drug clearance profiles with samples from didemnin B-treated patients.
Raybould
T J
TJ
Hawaii Biotechnology Group, Inc., Immunochemistry Division, Aiea 96701.
Grothaus
P G
PG
Simpson
S B
SB
Bignami
G S
GS
Lazo
C B
CB
Newman
R A
RA
D000970:Antineoplastic Agents / Q000097:blood / Q000276:immunology / Q000627:therapeutic use; D047630:Depsipeptides; D005069:Evaluation Studies as Topic; D006241:Haptens; D006433:Hemocyanins; D006801:Humans; D007124:Immunoenzyme Techniques; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy; D010456:Peptides, Cyclic / Q000097:blood* / Q000276:immunology / Q000627:therapeutic use; D012710:Serum Albumin, Bovine
D000970:Antineoplastic Agents; D047630:Depsipeptides; D006241:Haptens; D010456:Peptides, Cyclic; D012710:Serum Albumin, Bovine; C030051:didemnins; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin