Administration of OKT3 as a two-hour infusion attenuates first-dose side effects.
BACKGROUND
Use of the murine CD3 monoclonal antibody OKT3 is limited by first-dose side effects, which are thought to be caused by the release of inflammatory mediators. Because these processes might be influenced by the speed of administration, we compared a 2-hr OKT3 infusion with the bolus infusion usually applied nowadays.


METHODS
Eighteen renal allograft recipients were prophylactically treated with OKT3 and randomized to receive the first dose either as a 2-hr infusion or as an intravenous bolus infusion. Clinical side effects score and the occurrence of complement activation, cytokine release, and activation of neutrophils were determined.


RESULTS
Two-hour infusion of OKT3 completely prevented the occurrence of dyspnea, reduced the incidence of other side effects, and attenuated complement activation. Cytokine release and depletion of peripheral blood lymphocytes were similar in both groups.


CONCLUSIONS
Thus, complement activation seems to play an additional role in the development of side effects after the first OKT3 dose.
Buysmann
S
S
Renal Transplant Unit, Department of Internal Medicine, Academic Medical Center, University of Amsterdam, The Netherlands.
Hack
C E
CE
van Diepen
F N
FN
Surachno
J
J
ten Berge
I J
IJ
D000706:Anaphylatoxins / Q000378:metabolism; D000818:Animals; D003167:Complement Activation / Q000187:drug effects; D015926:Complement C3a / Q000031:analogs & derivatives / Q000378:metabolism; D004334:Drug Administration Schedule; D004417:Dyspnea / Q000139:chemically induced* / Q000517:prevention & control; D007262:Infusions, Intravenous; D016030:Kidney Transplantation / Q000009:adverse effects; D051379:Mice; D016853:Muromonab-CD3 / Q000008:administration & dosage / Q000627:therapeutic use*; D018375:Neutrophil Activation / Q000187:drug effects
D000706:Anaphylatoxins; D016853:Muromonab-CD3; C044541:complement C3a, des-Arg-(77)-; D015926:Complement C3a