Immunopharmacodynamic profiles in children with renal allografts receiving cyclosporine therapy.
Eleven renal transplant patients between the ages of 4 and 19 years, on a single daily oral dose of cyclosporine (CsA) and either a low oral dose or no dose of prednisone, had venous blood drawn at periodic intervals throughout a 24-hour period. CsA levels were measured by whole blood radioimmunoassay. All the patients had similar patterns of CsA pharmacokinetics with a single peak blood level at two to eight hours after the drug was given. Plasmas separated from the bloods at 37 degrees C were added to third party mixed lymphocyte reactions (MLR). The kinetics of suppression of the MLR by serial plasmas did not follow the CsA levels. Instead, we observed patterns of suppression similar to those that have been described in adults. Five patients had pattern I with two peaks of plasma-mediated MLR suppression, and had no rejection episodes. Two of the patients had pattern II with only one peak of MLR suppression, and both had episodes of acute rejection. One patient showed pattern III with a pleateau of MLR suppression, and has had no rejection episodes and no obvious CsA toxicity. Three patients showed pattern IV with a continuously low level of plasma-mediated MLR suppression throughout the day, and two of them have had severe rejection episodes. Immunopharmacodynamic profiling (IP) may prove to be useful in individualizing therapeutic regimens for patients with renal allografts treated with CsA.
Reisman
L
L
Department of Pediatrics, Mount Sinai School of Medicine, New York, NY 10029.
Lieberman
K V
KV
Martinelli
G P
GP
Bowles
K E
KE
Schanzer
H
H
Burrows
L
L
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003524:Cyclosporins / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D006084:Graft Rejection / Q000187:drug effects; D006801:Humans; D016030:Kidney Transplantation; D007959:Lymphocyte Culture Test, Mixed; D011241:Prednisone / Q000627:therapeutic use; D011446:Prospective Studies; D011863:Radioimmunoassay
D003524:Cyclosporins; D011241:Prednisone