The effect of graft function on FK506 plasma levels, dosages, and renal function, with particular reference to the liver.
Plasma FK506 was studied in 49 liver, 13 heart, 3 double-lung or heart-lung, and 21 kidney recipients. The levels were correlated with the drug doses used, kidney function, and liver function. In all varieties of recipients, there was an early rise in the FK506 plasma levels that occurred at the time of intravenous administration of the drug. At the same time or shortly after, there were increases in serum creatinine that were transitory except in liver recipients with continuing suboptimal graft function. The quality of hepatic function dominated all aspects of FK506 management in the liver recipients. Those who received well-functioning grafts could be given about the same drug doses as recipients of kidneys and the thoracic organs. Liver recipients with defective grafts had astronomical rises in plasma FK506, a high incidence of renal failure, and probably increased neurotoxicity. In kidney transplant recipients, the FK506 plasma levels and doses were essentially the same in patients with prompt versus delayed renal function. These studies have highlighted the necessity, first, of close pharmacologic monitoring of patients who are given FK506 in the presence of abnormal liver function, and second, of using smaller intravenous induction doses than in past practice.
Abu-Elmagd
K
K
Department of Surgery, School of Pharmacy, University of Pittsburgh, Pennsylvania.
Fung
J J
JJ
Alessiani
M
M
Jain
A
A
Venkataramanan
R
R
Warty
V S
VS
Takaya
S
S
Todo
S
S
Shannon
W D
WD
Starzl
T E
TE
D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology; D000998:Antiviral Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D016027:Heart Transplantation; D016041:Heart-Lung Transplantation; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D016030:Kidney Transplantation; D008099:Liver / Q000378:metabolism; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation; D011184:Postoperative Period; D011241:Prednisone / Q000627:therapeutic use; D016559:Tacrolimus
D000900:Anti-Bacterial Agents; D000998:Antiviral Agents; D003404:Creatinine; D011241:Prednisone; D016559:Tacrolimus