Muromonab CD‐3: A Review of Its Pharmacology, Pharmacokinetics, and Clinical Use in Transplantation

Abstract

Muromonab CD‐3 (OKT‐3) is a monoclonal antibody that is highly effective in the treatment of acute rejection in solid organ transplants. Due to its monoclonal nature, each molecule is identical because it is derived from a single antibody‐producing clone. OKT‐3 is administered only by intravenous injection and has a harmonic half‐life of approximately 18 hours. It binds specifically to the CD‐3 complex, which is involved in antigen recognition and cell stimulation, on the surface of T lymphocytes. Immediately after administration CD‐3‐positive T lymphocytes are abruptly removed from the circulation. The route of metabolism for OKT‐3 is not clear; it may be removed by opsonization by the reticuloendothelial system when bound to T lymphocytes, or by human antimurine antibody production. The agent has been effective in reversing corticosteroid‐resistant acute rejection in renal, liver, and cardiac transplant recipients. Its use in pancreatic and bone marrow recipients is inconclusive. OKT‐3 has a considerable number of initial side effects, and some life‐threatening reactions may occur. This drug should not be administered to any patient who is greater than 3% usual body weight because of the potential for the development of severe pulmonary edema. OKT‐3 may also be associated with a high rate of infection, especially of the viral type. The usual dose is 5 mg administered as an intravenous bolus over 2–4 minutes daily for 10–14 days. Approximately 85% of patients treated with OKT‐3 develop reactive human antimurine antibodies that, over time, may lead to tachyphylaxis and neutralization of the murine antibody OKT‐3. OKT‐3 is potent immunosuppressive agent and is an important prototype of future monoclonal antibodies.