Comparative study of cyclosporine and FK 506 dosage requirements in adult and pediatric orthotopic liver transplant patients.

Abstract

Cyclosporine (CyA) has been used in orthotopic liver transplantation (OLTx) for over 10 years, while FK 506 has been in use for the last 2 years1 at the University of Pittsburgh. It has been shown that CyA dosage in pediatric OLTx is higher compared to adult OLTx, possibly owing to rapid metabolism in children and/or poor absorption from Roux-en-Y loop often used for biliary reconstruction.2 It is also known that absorption of CyA is dependent on the presence of bile in the gut.3 We have shown FK 506 absorption does not change with the presence or absence of bile both in humans4,5 and in animals.6 We have also observed that the half-life of FK 506 in children is about two times smaller, the clearance is nearly two to four times more rapid, and the volume of distribution is 1.8 times higher as compared to adults with comparable liver function in the immediate posttransplant period (unpublished data). The present study compares how the above differences reflect in actual clinical practice following OLTx in adults and children, both in terms of intravenous (IV) and oral (PO) therapy. In addition, we also compared the trough levels of FK 506 (in plasma) and CyA (whole blood TDx) in adults and children.