Work

Bioassay of plasma specimens from liver transplant patients on FK 506 immunosuppression.

Year: 1990

Type: article

Abstract: Liver transplantation has been increasingly used to treat end-stage liver diseases since the introduction of CyA in combination with other immunosuppressive agents.1 Although CyA has a powerful immunosuppressive effect on allograft rejection, many transplant recipients still experience rejection episodes that are often irreversible. The nephrotoxicity of CyA in some recipients has necessitated the reduction of CyA dosage below effective levels. With liver recipients refractory to conventional immunosuppression or with CyA-induced nephrotoxicity, a first-phase clinical trial of a new immunosuppressive drug, FK 506, has been initiated at our institution.2 FK 506 was shown by in vitro and in vivo studies to be considerably more immunosuppressive than CyA.3–7 The successful outcome of the initial clinical studies on 14 liver transplant recipients2 has led to a formal clinical trial of FK 506 as the primary immunosuppressive agent in combination with low doses of steroids.8 Appropriate dosages of FK 506 are being determined to provide optimal immunosuppression without significant adverse side effects. The monitoring of blood levels of FK 506 is essential in these studies. This monitoring has become possible with an enzyme immunoassay (ELISA) using anti-FK 506 MoAbs. This assay was developed by Tamura et al9 and modified by Cadoff et al.10 FK 506 is a highly lipophilic macrolide (molecular weight 822).11 Although little is known about the metabolites of FK 506, recent studies have implicated the liver as the primary site of FK 506 metabolism.12 The objective of this study was to determine the relationship between plasma levels of FK 506 as measured by ELISA and by a bioassay based on the proliferative response of an alloreactive T cell line.

Source: PubMed