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Pharmacokinetics of FK506 in liver transplant recipients after continuous intravenous infusion

Jain, AB and Abu-Elmagd, K and Abdallah, H and Warty, V and Fung, J and Todo, S and Starzl, TE and Venkataramanan, R (1993) Pharmacokinetics of FK506 in liver transplant recipients after continuous intravenous infusion. Journal of Clinical Pharmacology, 33 (7). 606 - 611. ISSN 0091-2700

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Abstract

The first-dose pharmacokinetics of FK506 was studied in nine orthotopic liver transplant patients receiving continuous intravenous infusion of 0.15 mg/kg/day. Multiple blood samples were obtained during the infusion and plasma FK506 concentrations were measured by enzyme-linked immunosorbent assay. The plasma clearance ranged from 0.47 to 5.8 L/minute, and the half- life ranged from 4.5 hours to 33.1 hours. These results indicate the pharmacokinetics of FK506 to be highly variable between patients. FK506 is extensively distributed outside the plasma compartment. FK506 is extensively metabolized in the body, with less than 1% of the administered dose being excreted in the urine as unchanged FK506. The large variability in FK506 kinetics during the immediate postoperative period is attributed to the variability in the functional status of the liver in the transplant patients. Because of the long half-life of FK506, it takes more than 45 hours to reach steady-state concentrations after continuous infusion. Based on the estimated kinetic parameters, it appears that a combination of a bolus or a rapid infusion of .02 mg/kg with a continuous infusion of 0.05 mg/kg/day will provide and maintain a concentration of more than 2 ng/mL from the beginning of the drug treatment.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Jain, AB
Abu-Elmagd, K
Abdallah, H
Warty, V
Fung, J
Todo, S
Starzl, TEtes11@pitt.eduTES11
Venkataramanan, Rrv@pitt.eduRV
Centers: Other Centers, Institutes, Offices, or Units > Thomas E. Starzl Transplantation Institute
Date: 1 January 1993
Date Type: Publication
Journal or Publication Title: Journal of Clinical Pharmacology
Volume: 33
Number: 7
Page Range: 606 - 611
DOI or Unique Handle: 10.1002/j.1552-4604.1993.tb04712.x
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 0091-2700
Other ID: uls-drl:31735062125897, Starzl CV No. 1647
Date Deposited: 08 Apr 2010 17:28
Last Modified: 09 Dec 2017 12:55
URI: http://d-scholarship.pitt.edu/id/eprint/5033

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